Skin preparation for external use characterized by containing sugar derivative of alpha, alpha-trehalose

ABSTRACT

The present invention has an object to provide an external dermatological formulation having satisfactory blood flow-promoting effect, antiinflammatory effect, antibacterial effect, moisturizing effect, whitening effect, UV-absorbing effect, UV-scattering effect, antioxidant effect, hair growing effect, hair nourishing effect, emusifying effect, astringent effect, wrinkle-reducing effect, cell-activating effect and/or transdermal absorption-promoting effect with a satisfactory safety and skin feeling; The object is solved by providing an external dermatological formulation comprising a saccharide derivative of α,α-trehalose and one or more members selected from substances having any one of blood flow-promoting effect, antiinflammatory effect, antibacterial effect, moisturizing effect, whitening effect, UV-absorbing effect, UV-scattering effect, antioxidant effect, hair growing efect, hair nourishing effect, emulsifying effect, astringent effect, wrinkle-reducing effect, cell-activating effect and transdermal absorption-promoting effect.

TECHNICAL FIELD

The present invention is to provide an external dermatologicalformulation, which comprises a saccharide derivative of α,α-trehaloseand one or more members selected from substances having any one of bloodflow-promoting effect, antiinflammatory effect, antibacterial effect,moisturizing effect, whitening effect, UV-absorbing effect,UV-scattering effect, antioxidant effect, hair growing effect, hairnourishing effect, astringent effect, wrinkle-reducing effect,cell-activating effect and transdermal absorption-promoting effect; andto provide an external dermatological formulation which has acomfortable feeling, enhanced above effects, and insubstantial stickyfeeling.

BACKGROUND ART

The skins including the head skin may have troubles such as a roughskin, suntan, aging, liver spot, wrinkle and loss of hair due tointernal or external factors or aging. Many of these troubles areaccompanied by poor blood circulation and/or inflammation in the part orwhole of the skins. To solve such problems, usual externaldermatological formulations have been used in combination with asynthetic drug or natural extract having blood flow-promoting effect,antiinflammatory effect, antibacterial effect, moisturizing effect,whitening effect, UV-absorbing effect, UV-scattering effect, antioxidanteffect, astringent effect, wrinkle-reducing effect, cell-activatingeffect or transdermal absorption-promoting effect. However, suchingredients may not exert the desired effects when used alone or in alow dose. While, when used in a high dose, they may cause irritatingfeeling, unpleasant smell, insufficient extension and sticky feeling inthe skins. Further, when continuously used, they may cause thedermatitis and rough skin.

To solve these problems, Japanese Patent Publication (Kokai) No.128,136/94 discloses an external dermatological formulation enhanced inthe antiinflammatory effect, which contains α,α-trehalose and substancehaving an antiinflammatory effect or blood flow-promoting effect.Japanese Patent Publication (Kokai) No. 77,650/97 discloses a cosmetichaving a satisfactory spreading property without causing/inducing stickyfeeling, which contains trehalose, monosaccharides or sugar alcoholsthereof, and disaccharides or sugar alcohols thereof. The presentapplicant disclosed an applicability of α,α-trehalose or saccharidederivatives thereof for cosmetics in Japanese Patent Publication (Kokai)Nos. 143,876/95, 73,504/96 and 228,980/2000, and Japanese Patent No.3,182,679. However, these patent literatures never disclose any evidencethat saccharide derivatives of α,α-trehalose inhibits the reduction ofuncomfortable feelings such as sticky feeling, insufficient spreadingproperty and irritating feeling caused by substances having any one ofblood flow-promoting effect, antiinflammatory effect, antibacterialeffect, moisturizing effect, whitening effect, UV-absorbing effect,UV-scattering effect, antioxidant effect, hair growing effect, hairnourishing effect, astringent effect, wrinkle-reducing effect,cell-activating effect and transdermal absorption-promoting effect. Inaddition, they never disclose concretely any evidence that saccharidederivatives of α,α-trehalose enhance the effects of ingredientsapplicable to external dermatological formulation. They never disclosethat a saccharide mixture containing α-maltosyl α,α-trehalose and sugaralcohols as effective ingredients is more effective.

The present invention has an object to provide an externaldermatological formulation having a satisfactory safety and comfortablefeeling without sticky feeling, which is enhanced in one or more effectsof the substances selected from those having blood flow-promotingeffect, antiinflammatory effect, antibacterial effect, moisturizingeffect, whitening effect, UV-absorbing effect, UV-scattering effect,antioxidant effect, hair growing effect, hair nourishing effect,astringent effect, wrinkle-reducing effect, cell-activating effect andtransdermal absorption-promoting effect.

DISCLOSURE OF THE INVENTION

The present inventors have eagerly studied on use of saccharides toattain the above object. As a result, they revealed that saccharidederivatives of α,α-trehalose synergistically enhance the effects ofingredients for external dermatological formulation, such as substanceshaving any one of blood flow-promoting effect, antiinflammatory effect,antibacterial effect, moisturizing effect, whitening effect,UV-absorbing effect, UV-scattering effect, antioxidant effect, hairgrowing effect, hair nourishing effect, astringent effect,wrinkle-reducing effect, cell-activating effect and transdermalabsorption-promoting effect, without uncomfortable feeling such assticky feeling, irritating feeling and uncomfortable spreading property.Particularly, they revealed that the saccharide derivatives ofα,α-trehalose enhanced the substances having blood flow-promoting effectand/or antiinflammatory effect to prevent or improve rough skins,suntan, aging, liver spot, or wrinkle, and accomplished this invention.The present invention provides an external dermatological formulation,which is characterized in that it comprises substances having anyone ofblood flow-promoting effect, antiinflammatory effect, antibacterialeffect, moisturizing effect, whitening effect, UV-absorbing effect,UV-scattering effect, antioxidant effect, hair growing effect, hairnourishing effect, astringent effect, wrinkle-reducing effect,cell-activating effect or transdermal absorption-promoting effect, andit is enhanced in such effects. It also has a satisfactory feeling andsafety without sticky feeling, irritating feeling and uncomfortablespreading property, and excellent effect on preventing or curing roughskin, sunburn, liver spot and wrinkle.

BEST MODE FOR CARRYING OUT THE INVENTION

The term “external dermatological formulation” as referred to as in thepresent invention means an agent to be directly applicable for the skinssuch as of the face and body, mucosae, hair and head skin of human, petsor domestic animals for the purpose of preventing the rough skin,suntan, liver spot, wrinkle, inflammation, or aging, curing variousdiseases such as atopic diseases, allergic diseases, ulcers, injures andinfectious diseases, moisturizing, whitening, beauty treatment, hairnourishing or hair glowing. The above term includes cosmetics includingskin-care cosmetics, makeup cosmetics, body-care cosmetics, hair-carecosmetics, oral-care cosmetics, and fragrance cosmetics, quasi-drugs andpharmaceuticals, which are illustrated with cosmetic soaps, facial soap,shampoo, rinse, hair shampoo, cosmetics for hair, usual cream/milkylotions, cream for shaving, cosmetic lotions, eau de cologne, lotion forshaving, cosmetic oils, face powders, foundations, cheek rouge, eyebrowpencil, eye cream, eye shadow, mascara, perfume, sun cream, sun blockcream, sun lotion, sun block lotion, sun oil, sun block oil, nail cream,enamel, enamel remover, eyeliner, lipstick, lip cream, toothpaste, bathcosmetics, or preparations for curing various diseases. In addition, italso includes quasi-drugs or pharmaceuticals used in an manner ofapplying or adhering on skins or mucosae, such as ointments, cataplasmsand films, quasi-drugs or foods and beverages used orally such as oralrefrigerant. Further, it also includes groceries possible to contactwith and influence skins, such as soaps and detergents for washing,detergents for floors, cleansers, and detergents for kitchen.

The term “inflammation” as referred to as in the present invention meansinflammatory changes in epidermis such as of the head skins, mucosae andskins, mainly, and includes redness of the skins due to slight degree ofsunburn, stomatitis, acne, heat rash, rough and swelling of throat,itch, pain, generation of erythema, papule or bulla, generation ofulcer, and eczema. It properly involves stomatitis due to autoimmunediseases such as Sjögren's syndrome, clinical syndromes such as drymouth due to the stamatitis, and inflammation and bleeding of teethridges due to alveolar pyorrhea. Such inflammations are sometimes causedby external stimulations and/or factors of living bodies (includingconstitutional factors), or in combination thereof. The externalstimulations are illustrated with various chemical substances,cosmetics, metals, detergents or drugs, and further biological factorssuch as microorganisms, plants, animals and insects, and physicalfactors such as sunlight, heat, cold and dryness. The biological factorsinclude other factors due to regional disorders such as sweating,secretion of sebum and keratosis, or systemic disorders such as atopicdiseases, allergic diseases, infections, disorders in internal organssuch as digestive organs, liver, or kidney. The inflammations properlyinclude inflammations due to ingredients of external dermatologicalformulations.

The term “saccharide derivatives of α,α-trehalose” as referred to as inthe present invention includes any one or more non-reducingoligosaccharides having the α,α-trehalose structure and composed ofthree or more glucose residues. The external dermatological formulationof the present invention comprises one or more such oligosaccharides.Concretely, these saccharide derivatives of α,α-trehalose are composedof one α,α-trehalose molecule and either of mono-glucose residue,di-glucose residue, tri-glucose residue or tetra-glucose residue boundto both or either end of the α,α-trehalose molecule. The saccharidederivatives of α,α-trehalose, preferably used in the present invention,are composed of three to six glucose residues as previously disclosed bythe same applicant in Japanese Patent Publication (Kokai) Nos.143,876/95, 73,504/96 and 228,980/00, and Japanese Patent No. 3,182,679.Such saccharide derivatives are illustrated with mono-glucosylα,α-trehalose such as α-maltosyl α-glucoside and α-isomaltosylα-glucoside; di-glucosyl α,α-trehalose such as α-maltotriosylα-glucoside (alias α-maltosyl α,α-trehalose), α-maltosyl α-maltoside,α-isomaltosyl α-maltoside and α-isomaltosyl α-isomaltoside; tri-glucosylα,α-trehalose such as α-maltotetraosyl α-glucoside (alias α-maltotriosylα,α-trehalose), α-maltosyl α-maltotrioside, α-panosyl α-maltoside; andtetra-glucosyl α,α-trehalose such as α-maltopentaosyl α-glucoside (aliasα-maltotetraosyl α,α-trehalose), α-maltotriosyl α-maltotrioside andα-panosyl α-maltotrioside.

Such saccharide derivatives of α,α-trehalose can be produced byfermenting method, enzymatic method or organic synthetic method, and arenever restricted to specific origin or process. For example, thesaccharide derivatives can be directly prepared from starch materials orhydrolyzates thereof by the enzymatic methods disclosed by the sameapplicant in Japanese Patent Publication (Kokai) Nos. 143,876/95,73,504/96 and 228,980/00, and Japanese Patent No. 3,182,679. Inaddition, they can be prepared by reacting starch hydrolyzates rich insome kinds of oligosaccharides such as maltotetraose, maltopentaose,maltohexaose and maltoheptaose obtainable with a maltotetraose producingenzyme disclosed in Japanese Patent Publication (Kokai) No. 143,876/95,an α-amylase capable of efficiently producing maltopentaose disclosed inJapanese Patent Publication (Kokoku) No. 14,962/95 and a maltohexaosemaltoheptaose producing amylase disclosed in Japanese Patent Publication(Kokai) No. 236,478/95 with non-reducing saccharide producing enzymedisclosed in Japanese Patent Publication (Kokai) No. 143,876/95.Further, they can be prepared by reacting a solution containing starchor hydrolyzates thereof and α,α-trehalose with an enzyme capable oftransferring glycosyl group such as cyclodextrin glucanotransferase. Theresulting reaction mixture obtained by the above method can be used as asaccharide solution containing saccharide derivatives of α,α-trehalose.Optionally, they can be partially or highly purified. Such preparationprocesses, using easily and cheaply available starch materials, areadvantageously used in view of industrial production because of theirsufficient production yield and low cost.

When applied to subjects, the saccharide derivatives having a trehalosestructure at the end of the molecules more effectively improve skinfeeling and enhances the blood flow-promoting effect, antiinflammatoryeffect, antibacterial effect, moisturizing effect, whitening effect,UV-absorbing effect, UV-scattering effect, antioxidant effect, hairgrowing effect, hair nourishing effect, astringent effect,wrinkle-reducing effect, cell-activating effect and transdermalabsorption-promoting effect, and has strong moisturizing property amongthe saccharide derivatives of α,α-trehalose described above.Particularly, saccharide mixtures containing α-maltotriosyl α-glucoside(alias α-maltosyl α,α-trehalose) as a main ingredient and one or moresaccharides selected from the group consisting of α-maltotriosylα-glucoside (alias α-glucosyl α,α-trehalose), α-maltotetraosylα-glucoside (alias α-maltotriosyl α,α-trehalose), and α-glucosylα-glucosides other than the saccharide derivatives of α,α-trehalosedescribed above. The amount of α-maltosyl α,α-trehalose in each of thesaccharide mixtures is 5% by weight or more (hereinafter, “% by weight”is simply represented by “%”), preferably 10% or more, more preferably20% or more, and most preferably 50% or more.

Among the above saccharides, α-maltosyl α-glucoside and α-maltotetraosylα-glucoside in a crystalline form are disclosed in Japanese Patent No.3,182,679 and Japanese Patent Publication (Kokai) No. 228,980/00. Toexert the desired effect according to this invention, such crystallinesaccharides are preferably used after changed into amorphous states suchas liquid states, syrupy states, and glassy paste or solid states.α-Maltotetraosyl α-glucoside, as one of the easily crystallizedsaccharide derivatives of α,α-trehalose, can be used for toothpaste asan abrasive with a low hardness after partially or completely formed ina crystal. In addition, it also can be used as a UV-scattering agent forsun-protect and as a base ingredient for finishing cosmetics such as eyeshadow, mascara, or foundation with stabilizing function for colorantsin an external dermatological formulation.

As described above, the saccharide derivatives of α,α-trehalose used inthe present invention are preferable in an amorphous state. It can beused in any form such as syrup, masquitte, paste, powder, solid, granuleand tablet as long as it contains one in an amorphous form. Ifnecessary, they can be used in combination with fillers, excipients orbinders.

The saccharide derivatives of α,α-trehalose can be incorporated into theformulation of the present invention at a desired processing step fromprocessing of raw materials before obtaining the final products byconventional methods. Examples of such methods are mixing, kneading,resolving, melting, dispersing, suspending, emulsifying, forming inversemicelle, penetrating, crystallizing, scattering, applying, spraying,injecting, immersing, solidifying and holding.

The amount of saccharide derivatives of α,α-trehalose in the formulationof the present invention is not specifically restricted as long as it isenough to be capable of enhancing any one of blood flow-promotingeffect, antiinflammatory effect, antibacterial effect, moisturizingeffect, whitening effect, UV-absorbing effect, UV-scattering effect,antioxidant effect, hair growing effect, hair nourishing effect,astringent effect, wrinkle-reducing effect, cell-activating effect andtransdermal absorption-promoting effect. It is usually about 0.01% ormore, preferably aout 0.1% or more, more preferably about 0.2% or moreto the weight of a final product, on a dry solid basis. Usually, in thecase of less than about 0.01%, it is insufficient to enhance the effectsby these substances even when used in combination with one or moresubstances. The upper limit of the amount of the saccharide derivativesof α,α-trehalose is not specifically restricted as long as they do notaffect the quality and function of objective external dermatologicalformulations.

The saccharide derivatives of α,α-trehalose can be incorporated aloneinto the formulation of the present invention. Optionally, a saccharidemixture, containing other saccharides and/or sugar alcohols togetherwith the saccharide derivatives of α,α-trehalose (hereinafter, it isdescribed as “saccharide mixture containing saccharide derivatives ofα,α-trehalose”), can be used. Examples of such other saccharides areglucose, isomaltose, maltose, oligosaccharide and dextrin, which areproduced from starch materials in the preparation of the saccharidederivatives of α,α-trehalose. Particularly, the saccharide mixturecontaining sugar alcohols together with saccharide derivatives ofα,α-trehalose produced by hydrogenating a saccharide mixture containingreducing saccharides together with saccharide derivatives ofα,α-trehalose to convert the reducing saccharide into sugar alcohols,has a satisfactory moisturizing effect and a moderate viscosity, andinhibits sticky feeling of external dermatological formulations,improves skin feeling, and imparts gross in the skins and hairs. Whenapplied to the skins, it gives a satisfactory skin feeling differingfrom conventional base cosmetics containing glycerin. In addition, it iseffective on improving the holding property of cosmetics includingmoisturizing property. Particularly, a saccharide mixture, containing20% or more, preferably 50% or more, more preferably 50-70% ofα-maltosyl α,α-trehalose; 5-25% of total other saccharide derivatives ofα,α-trehalose; 5-45%, preferably 25-45% of sugar alcohols selected fromsorbitol and sugar alcohols of maltooligosaccharides, is preferable inview of enhancing the effect of other ingredients and showingsatisfactory moisturizing effect and skin feeling. Maltitol,maltotriitol and/or maltotetraitol are more preferable among sugaralcohols of maltooligosaccharides.

The saccharide derivatives of α,α-trehalose also have a cell-protectingeffect against external stress such as heat, UV and dryness, and alsohave a cell-activating effect. Therefore, they improve the metabolism ofthe skins, mucosae or head skins damaged by UV or other factors orsuffered from roughness or inflammation, when used alone or asingredient for an external dermatologic formulation. Further, theyinhibit the roughness, aging and inflammation and promote the recoveryfor the normal skins, mucosae or head skins by inhibiting the productionof inflammatory cytokines including tumor necrosis factor (hereinafter,designated as “TNF-α”) and interleukin-1 and the expression ofintercellular adhesion molecules. Furthermore, they lower theirritations due to various ingredients contained in the externaldermatologic formulation and physical irritations when applied to theskins. Therefore, the external dermatological formulation of the presentinvention can be advantageously used even if applied to a painful skin,including the skins, mucosae or head skins, which are suffered frominflammation due to sunburn or other disorders. The saccharidederivatives of α,α-trehalose of the present invention make the skins orhairs smooth in such a manner of coating surface of the skins, mucosaeor hairs. They also impart soft feelings and textures thereof,strengthen barrier function thereof and protect surface of skins orcuticle on surfaces of damaged hair. In addition, they have anantielectrostatic effect. Therefore, they can be advantageously used asa protectant for the hairs, hair roots, head skins, skins or mucosae; asmoothing agent; a gross imparting agent; a conditioning agent; anantielectrostatic agent; or a base, for hair-coloring agent. Thesaccharide derivatives of α,α-trehalose or saccharide mixture containingthe same are soluble in various substances used in externaldermatological formulations such as emulsifiers described below,solvents including ethanol, 1,3-butylene glycol, propylene glycol,concentrated glycerin, dipropylene glycol or 1,2-pentanediol, polyolsincluding sorbitol or maltitol, and synthetic polymers includingpolyethylene glycol (molecular weight 400-6,000) or carboxyvinylpolymer.They enable to prepare more homogenous and fine emulsified particleswhen used in creams with substances having emulsifying effect comparedwith the use of glycerin alone because they effectively reduce surfacetension without forming a milkiness and a precipitation in spite of alower solvent activity than glycerin. When used in a cleansing foam,shampoo or rinse, they impart elasticity to the produced foam, increasethe production of foam, retain the produced foam, the saccharidederivatives of α,α-trehalose inhibit physical stimulation of theproduced foam against the skins. Therefore, the external dermatologicalformulations containing them are used for cleaning the skins easily andcomfortably, and are capable of clearly removing dirt from inner poreswith dense forms and giving both of clear feeling and moisture to theskins after application. The saccharide derivatives of α,α-trehalose orsaccharide mixture containing the same of the present invention have theeffects on the inhibition of the oxidation and/or deterioration oflipids, or the stabilization and antioxidation of lipid membranes ofliposomes or cells. In addition, since they inhibit the oxidation,decomposition, browning or discoloration of various substancesacceptable for external dermatological formulations as well as thegeneration of foreign tastes and foreign smells, they are useful forexternal dermatological formulations containing substances easilyoxidized, browned, or discolored. Examples of such substances aresubstances having emulsifying effect such as amino acid type detergents;colorants such as natural colorants and synthetic colorants; perfumeriessuch as floral perfumeries; ascorbic acid; ascorbic acid 2-glucoside;tannin liquids; honey; beeswax; propolis; and amino acids. Therefore,they are used as ingredients for external dermatological formulationswithout sticky feeling, which can be advantageously used as moisturizingagent, moisture controlling agent, quality keeping agent,cell-protecting agent, cell-activating agent, foam-quality improvingagent, foam-quality controlling agent, stabilizer, browning inhibitoryagent, discoloration inhibitory agent, antioxidant for lipids,aroma-retaining agent.

The saccharide derivatives of α,α-trehalose of the present inventionhave no irritation and a high safety. They are hardly assimilated byanaerobitic resident bacteria in the skins or mouths, such asLactobacilus pentosus, Propionibacterium acnes and Streptococcus mutans.Therefore, they can be advantageously used as ingredients for anexternal dermatological formulation in order to treat bacterial skindisorders such as acnes, or used as toothpaste.

Any quality or quantity of substances, having blood flow-promotingeffect, antiinflammatory effect, antibacterial effect, moisturizingeffect, whitening effect, UV-absorbing effect, UV-scattering effect,antioxidant effect, hair growing and hair nourishing effect, astringenteffect, wrinkle-reducing effect, cell-activating effect or transdermalabsorption-promoting effect, can be used for the external dermatologicalformulation of the present invention as long as they do not affect thedesired effects. According to desired use, they can be used alone or incombination with two or more substances. If necessary, two or moresubstances having the same effect can be used in combination.

Examples of such substances having blood flow-promoting effect are plantor plant ingredients such as sialid, ginseng, ginkgo, ginger, garlic,angelica, arnica, fennel, plectranthi herba, Nasturtium officinale,chamomile, Roman chamomile, carrot, gentian, burdock, rice, crataegifructus, “shiitake”, Crataegus oxyacantha, juniper, Cnidium rhizome,thyme, clove, citrus unshiu peel, Japanese angelica root, persicaesemen, Paulownia bark, butche's broom, grape, peony, horse chestnut,balm mint, Citrus junos, coix seed, rosemary, rose hips, citrus unshiupeel, Japanese angelica, peach, apricot, walnut, horsetail, calamusroot, aloe, Plectranthi herba, gentian, capsicum and Citrus junos,hesperetin, hesperidin, glycosyl hesperidin, quercetin, rutin, glycosylrutin, naringenin, naringin, glycosyl naringin, esculetin, esculin,glycosyl esculin, acetylcholine, carpronium chloride, diphenhydraminehydrochloride, γ-oryzanol, 1-menthol, cepharanthine, vitamin E orvitamin E derivatives including d-δ-tocopherol, dl-α-tocopherol,dl-α-tocopherol acetate, dl-α-tocopherol linoleate, dl-α-tocopherolnicotinate, dl-α-tocopherol succinate and vitamin E nicotinate,minoxidil, nicotinamide, vanillylamide nonylate, carpronium chloride, orcarbon dioxide. The amount of the substance is not specificallyrestricted as long as the saccharide derivatives of α,α-trehalose arecapable of enhancing the effect of the above substances having bloodflow-promoting effect alone or in combination with other ingredients. Itis usually 0.001-5%, preferably 0.01-2% to the total amount of theexternal dermatological formulation. In the case of less than 0.001%,they are not expected to exert the desired effect. In the case of morethan 5%, they are not dose-dependently effective. When used in a hairtonic containing these substances as effective ingredients, the amountof the substances is not specifically restricted as long as thesaccharide derivatives enhance the hair-growing effect, and it isusually 0.0001-5%, preferably 0.002-3%. The term “plant or plantingredient” as referred to as in the present invention means crushedmaterials from plant bodies such as leaves, stems, roots, flowers,fruits and bark; and extracts such as of essential oils, oils, fats andtinctures, obtained by treating with water, methanol, ethanol, ether,ethyl acetate, acetone or butylene glycol form plant materials. Theresulting materials are optionally purified roughly or completely. Theterm “substances having blood flow-promoting effect” as referred to asin the present invention includes substances having the effect onexpanding the blood vessels to promote blood circulation. In addition,it also includes substances having the effect on inducing a factorhaving blood flow-promoting effect with a local administration. Examplesof such substances are capsoci tincture, zingiberis tincture, kantiristincture and wanyl norylate.

The term “substances having antiinflammatory effect” as referred to asin the present invention includes allantoin or derivatives thereof suchas allantoin acetyl-dl-methionine, allantoin chlorhydroxy aluminum,allantoin dihydroxy aluminum or allantoin polygalacturonate;glycyrrhetin or derivatives thereof such as glycyrrhetinic acid,glycyrrhizinic acid, allantoin glycyrrhetinate, glyceringlycyrrhetinate, stearyl glycyrrhetinate, glycyrrhetinyl stearate,disodium 3-succinyloxyglycyrrhetinate, dipotassium glycyrrhizinate,monoammonium glycyrrhizinate; pantothenic acid or derivatives thereofsuch as pantothenic acid, pantothenyl alcohols, pantothenyl ethylethers, acetyl pantothenyl ethyl ethers, benzoilpantothenylethyl ethers,calciumpantothenate, sodium pantothenate, acetyl pantothenyl ethylethers, pantothenyl ethyl ether benzoate, and pantethine; vitamin E orderivatives thereof such as vitamin E, d-δ-tocopherol, dl-α-tocopherol,dl-α-tocopherol acetate, dl-α-tocopherol linoleate, dl-α-tocopherolnicotinate, and dl-α-tocopherol succinate; L-ascorbic acid orderivatives thereof such as L-ascorbic acid, L-ascorbic acid glycosideincluding L-ascorbic acid 2-glucoside, acyl derivatives of L-ascorbicacid glycoside, ascorbyl tetrahexyldeconate, ascorbic acid tocopherolphosphate diesthers, L-ascorbic acid sulfate esthers, ascorbyldipalmitate, ascorbyl palmitate, stearyl L-ascorbate, L-ascorbylphosphate, ethyl L-ascorbate, acyl derivatives, alkali metal or alkalineearth metal salts thereof; pyridoxine hydrochloride; menthol; biotin;camphor; turpentine; zinc oxide; azulene; guaiazulene and derivativesthereof; mefenamic acid or derivatives thereof; phenylbutazone orderivatives thereof; indomethacin or derivatives thereof; ibuprofen orderivatives thereof; ketoprofen or derivatives thereof; ε-aminocapronicacid; sodium diclofenac; diphenhydramine; tranexamic acid or derivativesthereof; dexamethasone; cortisone or esthers thereof; hydrocortisone oresthers thereof; adrenal cortical hormone such as prednisone andprednisolone; antihistamic agent; rose fruit; Bistorta Major; turmeric;Hypericum erectum; phellodendron bark; glycyrrhiza; Lonicera japonica;watercress; comfrey; acanthopanacis bark; sage; lithospermum root; whitebirch; tea leaf; tian cha; Calendula officinatis; elderberry; Typhaangustifolia; Sapindus mukurossi, eucalyptus extract, broccoli, Japaneseangelica root, loquat, labiate, chamomile, wormwood, aloe, ginseng,indigo, phellodendron bark powder, Myrica rubra bark, gambir, sweethydrangea leaf, Althea officinalis root, arnica, echinacea, Plectranthiherba, scutellaria root, barley, St. John's wort, orange, Japanesevalerian, Roman chamomile, Artemisia caplillaris, cucumber, gardenia,Sasa albo-marginate, gentian, geranium herb, burdock, Xanthoxylumpiperitum, linden, peony root, ivy, juniper, peppermint, Cnidiumrhizome, sialid, sage, mori cortex, jujube, thyme, rose hips, Benincasaesemen, Calendula officinalis, persicae semen, houttuynia, cordata,Potantilla tormentilla, parsley, mint, nettle, sandalwood, Butcher'sbloom, grape, safflower, peony, linden, horse chestnut, peach,cornflower, wormwood, lavender, rosemary, carrot and Japanese angelicaroot. The amount of the substances is not specifically restricted aslong as the saccharide derivatives of α,α-trehalose are capable ofenhancing the effect of the above substances having antiinflammatoryeffect against dermatitis alone or in combination with other ingredient.It is usually 0.001-5%, preferably 0.01-3% to the total amount of theexternal dermatological formulation. In the case of less than 0.001%,they are expected to exert the desired effect. In the case of more than5%, they are not dose-dependently effective. When the ingredients areknown to be in plant tissues, for example, glycyrrhizin in glycyrrhiza,they are properly prepared as extracts of plants containing thereof tobe added to the present formulation.

The external dermatological formulation of the present inventioncontains one or more substances having any one of antibacterial effect,moisturizing effect, whitening effect, UV-absorbing effect,UV-scattering effect, antioxidant effect, hair growting efect, hairnourishing effect, astringent effect, wrinkle-reducing effect,cell-activating effect and transdermal absorption-promoting effect aswell as the above substances having blood flow-promoting effect and/orantiinflammatory effect. It can contain these substances together withthe above substances. Optionally, it contains two or more substanceshaving the same effect or physical property.

The term “substances having anti-bacterial effect” is not specificallyrestricted and can be selected from substances having antibacterialeffect acceptable to external dermatological formulations substanceshaving antibacterial effect. Example of such substances are loweralcohols such as ethanol; benzoic acid or salts thereof; benzoic acidesters; alkyl diaminoglycine hydrochloride; photosensitizing dye such aspionin (Kanko-so No. 201); chlorcresol; chlorbutanol; salicylic acid orsalts thereof; sorbinic acid or salts thereof; sorbinic acid esters;dehydroacetate or salts thereof; trichlorohydroxy phenyl ethers; paraoxybenzoic esthers; sodium paraoxy benzoate; phenoxy ethanol; phenol;sodium rauryl aminoethyl glycine; resorcin; zinc-ammonia-silversubstitutional zeolite; pantothenyl ethyl ethyl benzoate; isopropylmethyl phenol; cetylpyridium chloride; benzalkonium chloride;benzethonium chloride; chlorhexidine hydrochloride; orthophenyl phenol;sodium orthophenyl phenoxide; chlorhexidine gluconate, cresol,chloramine-T, chlorxylenol, chlorphenesin, chlorhexidine,1,3-dimethylol-5,5-dimethlhydantoin, alkyl isoquinoliniumbromide,thianthol, thymol, trichloro carbanilide, parachlorphenol, halocarban,hinokithiol, zinc pyrithione, methylchloroisothiazolinon/methlisothiazolin solution, N,N″-methylenebis[N′-(hydroxymethyl-2,5-dioxy-4-imidazolinyl)urea], 2-(p-dimethylaminostyryl)-3-heptyl-4-metyl-thiazolinium iodide, imidazolidinyl urea,dimethylol dimethyl hydantoin, glutaraldehyde, jamal II, bisabolol,chlorhexidine gluconate, isopropyl methyl phenol, phenoxy ethanol, orplants or components thereof having an antibacterial effect such ashinokithiol, tea oil, propolis, Sapindus mukurossi, asparagus, aloe,gingko, turmeric, echinacea, Plectranthi herba, Scutellaria radix,Coptis rhizome, Hypericum erectum, clusiaceous, orange, Artemisiacapillaris, gardenia, Sasa albo-marginate, Sophora angustifolia,grapefruit, Geranium thunbergii, Xanthoxylum piperitum, lithospermumroot, labiate, white birch, Lonicera japonica, Achillea millefolium,peppermint, Cnidium rhizome, sage, mori cortex, thyme, clove, Calendulaofficinalis, peony, hop, mint, peach, eucalyptus, lavender, rose hips,rosemary, wormwood, peony root, calamus and Saponaria officinalis. Theamount of the substances is not specifically restricted as long as thesaccharide derivatives of α,α-trehalose are capable of enhancing theeffect of the above substances having antibacterial effect alone or incombination with other ingredients. It is usually 0.0001-3% to totalamount of the external dermatological formulation. In the case of lessthan 0.0001%, they are expected to exert the desired effect. In the caseof more than 2%, they are not dose-dependently effective.

The term “substances having moisturizing effect” as referred to as inthe present invention includes mucopolysaccharides or derivativesthereof and salts thereof such as hyaluronic acid, chondroitin sulfate,delmatan sulfate, heparan sulfate and heparin; ceramide; peptides,proteins or hydrolyzates thereof such as collagen, elastin, fibronectin,keratin, gelatin and casein; amino acids or derivatives thereof such asglycine, alanine, valine, serine, threonine, methionine, phenylalanine,leucine, tyrosine, proline, isoleucine, tryptphan, hydroxyproline,theanine, ornithine, citrulline, asparagine, aspartic acid, glutamine,glutamic acid, arginine, histidine, lysine, hydroxylysine, cysteine,cystine, acyl glutamate and γ-polyglutamic acid; pyrrolidone carbonate;pearl essence; reducing or non-reducing saccharides such as powderstarch hydrolyzates, xylose, glucose, fractose, maltose, sucrose,lactose, paratinose, α,α-trehalose, α,β-trehalose (neotrehalose),β,β-trehalose (isotrehalose), isomerized sugar, honey, maple sugar,brown sugar, glycosyl sucrose-containing syrup, maltooligosaccharide,dextrin, isomaltooligosaccharide, galactooligosaccharide,fractooligosaccharide, nigerooligosaccharidel, galactosyl glucoside,lactosucrose, cyclic tetrasaccharide and/or derivatives thereofdisclosed by the present applicant in International Patent PublicationNos. WO02/24,832, WO02/10361 and WO02/072594 and Japanese PatentApplication No. 305,821/2000 specification, and starch; sugar alcoholssuch as erythritol, pentaerythritol, sorbitol, xylitol, maltitol,isomaltitol, lactitol and panitol; gums such as pullulan, levan, sodiumarginate, agar, gum Arabic, guar gum, tragacanth gum, xanthane gum,carrageenan and locust bean gum; water-soluble polymers such as pectin,methyl cellulose, carboxy methyl cellulose, polyvinyl alcohol, polyvinylpyrrolidone, polydextrose and polyacrylic acid; polyols such as sugaresthers, dextrin derivatives, glycerin, 1,3-butylene glycol,1,4-butylene glycol, dipropylene glycol, polyethylene glycol, propyleneglycol and amylene glycol; seaweeds such as coralline; plants orextracts thereof having moisturizing effect such as aloe, hamamelis,Xanthoxylum piperitum, Artemisia vulgaris, kava-kava, Asian ginseng,aloe, nettle, fennel, witch hazel, turmeric, Lotus corniculatus,Phellodendron amurense, Hypericum erectum, rice, chamomile, Artemisiacapillaris, kiwi, cucumber, Sophora angustifolia, grape, gardenia,comfrey, Saponaria officinalis, rehmannia root, labiate, peony root,white birch, horsetail, linden, sage, sialid, Cnidium rhizome, mulberry,soybean, thyme, Japanese angelica root, Calendula officinalis, parsley,coix seed, Butcher's bloom, loofah, hop, horse chestnut, balm mint,peach, saxifrage, bramble, lavender, Astragalus sinicus, rose, Rosemultiflora, rosemary, glycyrrhiza, tea leaf (green tea, black tea,oolong tea), lily, barley, wheat, apricot, oat, lithospermum root,lemon, quince, orange, strawberry, safflower, gentian, mint, spearmint,peppermint, Sapindus mukurossi, eucalyptus, Lamium album, pine,cornflower, Sanguisorba officinalis, avocado, seaweed, grapefruit,prune, lime, Citrus iunos, Coptis rhizome, cypress, peony, olive,sunflower, jojoba, macadamia nut, Limnanthes alba, camellia, almond,cacao and sesame. The amount of the substances is not specificallyrestricted as long as the saccharide derivatives of α,α-trehalose arecapable of enhancing the effect of the above substances havingmoisturizing effect alone or in combination with other ingredients. Itis usually 0.1-40%, preferably 0.5-20% to total amount of the externaldermatological formulation.

Particularly, the saccharide derivatives of α,α-trehalose of the presentinvention more strongly improve the moisturizing effect and skin feelingin combination with hyaluronic acid or mucopolysaccharides, moreparticularly hyaluronic acid, among the above substances. Hyaluronicacid used in the present invention is restricted to special molecularweight as long as it is enhanced in its moisturizing effect bysaccharide derivatives of α,α-trehalose. The molecular weight ofhyaluronic acid is usually 600,500,000, preferably 800,200,000.

The term “substances having whitening effect” includes L-ascorbic acidderivatives and/or alkali metal or alkaline earth metal salts thereofsuch as L-ascorbic acid, L-ascorbic acid glycosides including L-ascorbicacid 2-glucoside, acyl derivatives of L-ascorbic acid 2-glycoside,ascorbyl tetrahexyldeconate, ascorbic acid tocopherol phosphatediesther, L-ascorbic acid sulfate esther, ascorbyl dipalmitate, ascorbylpalmitate, stearyl L-ascorbate, L-ascorbyl phosphate, ethyl L-ascorbate,acyl derivatives thereof; lactic acid, kojic acid, ellagic acid orderivatives thereof and/or alkali metal salts or alkaline earth metalsalts, tranexamic acid, phytic acid, glutathione, hydroquinone orderivatives thereof including arbutin, plants or ingredients thereofhaving whitening effect such as chamomilla ET, “RUCINOL®”(4-n-Butylresorcinol), chamomile extract, brown sugar extract, arbutin(a kind of glycosyl hydroquinone), glycyrrhiza, mori cortex, uva-ursi,bilberry extract, houttuynia herb extract, deer horn shape ganodermalucidum extract, iris, clove, turmeric, capsicum, karela, aloe, tealeaf, glycyrrhiza, scutellaria root, chamomile, mori cortex, puerariaroot, Xanthoxylum piperitum, moutan bark, gingko, rose fruit, Coptisrhizome, Hypericum erectum, gardenia, Sophorae radix, rice, rice bran,asiasarum root, peony root, cnidium root, mori cortex, tea leaf,Japanese angelica root, Calendula officinalis, hamamelis, safflower,Amethyst sage, gambir, hackberry, Diospyros kaki, sage, Japanese radish,azalea, parsley, hop and coix seed; animal ingredients such as placentaextract; and inorganic substance such as sulfur. The amount of thesubstances is not specifically restricted as long as the saccharidederivatives of α,α-trehalose are capable of enhancing the effect of theabove substances having whitening effect alone or in combination withother ingredient. It is usually 0.001-5%, preferably 0.01-3% to totalamount of the external dermatological formulation. In the case of lessthan 0.001%, they are expected to exert the desired effect. In the caseof more than 5%, they are not dose-dependently effective.

The term “substances having antioxidant effect” as referred to as in thepresent invention includes plants or plants ingredients havingantioxidant effect such as vitamin A or derivatives thereof, vitamin Bor derivatives thereof, L-ascorbic acid or derivatives thereof, vitaminD or derivatives thereof, vitamin E or derivatives thereof, dibutylhydroxy toluene, butyl hydroxy anisole, superoxide dismutase, mannitol,carotenoids, astaxanthin, rutin or derivatives thereof, rutin,hesperidin, quercetin, catechin, epicatechin, epigallocatechin, orderivatives thereof including saccharide derivatives, gallic acid orderivatives thereof, glutathione or derivatives thereof, glutathione,β-carotenes or derivatives thereof, ubiquinol, flavonoids, polyphenols,sweet hydrangea leaf, turmeric, rose fruit, echinacea, Scutellaria root,Hypericum erectum, Chinese gall nut, Geranium thunbergii, rice, ricebran, comfrey, Xanthoxylum piperitum, labiate, peony root, soybean,“Natto” (soybeans fermented in their own bacteria), tea leaf, clove,loquat, peony, horse chestnut, saxifrage, rooibos, rosemary, spirulina,chlorella and dunaliella. In addition, they include bilirubin,cholesterol, tryptophan, histidine, thiotaurine and hypotaurine. Theamount of the substances is not specifically restricted as long as thesaccharide derivatives of α,α-trehalose are capable of enhancing theeffect of the above substances having antioxidant effect alone or incombination with other ingredient. It is usually 0.0001-5%, preferably0.001-2% to total amount of the external dermatological formulation. Inthe case of less than 0.0001%, they are expected to exert the desiredeffect. In the case of more than 5%, they are not dose-dependentlyeffective. The saccharide derivatives of α,α-trehalose inhibit thebrowning of L-ascorbic acid. Therefore, more amount of L-ascorbic acidor derivatives thereof can be used for external dermatologicalformulation in combination the saccharide derivatives of α,α-trehalose.

The term “substances having UV-absorbing effect” as referred to as inthe present invention include benzoate compounds such asparaaminobenzoic acid (PABA), PABA monoglycerin esther, N,N-dipropoxyPABA ethyl esther, N,N-diethoxy PABA ethyl esther, N,N-dimethyl PABAethyl esther, N,N-dimethyl PABA butyl esther; anthranilate compoundssuch as homomenthyl-N-acetyl anthranilate; salicylate compounds such asamyl salicylate, menthyl salicylate, homomenthyl salicylate, octylsalicylate, phenyl salicylate, benzyl salicylate, p-isopropanol phenylsalicylate; cinnamate compounds such as octyl cinnamate,ethyl-4-isopropylcinnamate, methy-2,5-diidopropylcinnamate,ethy-2,4-diisopropylcinnamate, methy-2,4-diisopropylcinnamate,propyl-p-methoxy cinnamate, isopropyl-p-methoxy cinnamate,isoamyl-p-methoxy cinnamate, octyl-p-methoxy cinnamate(2-ethylhexyl-p-methoxy cinnamate), 2-ethoxyethy-p-methoxycinnamate,cyclohexyl-p-methoxy cinnamate, ethyl-α-cyano-β-phenyl cinnamate,2-ethylhexyl-α-cyano-β-phenyl cinnamate and glycerylmono-2-ethylhexanoyl-diparamethoxycinnnmate; benzophenone compound suchas 2,4-dihydroxy benzophenone, 2,2′-dihydroxy-4-methoxy benzophenone,2,2′-dihydroxy-4,4′-dimethoxy benzophenone, 2,2′,4,4′-tetrahydroxybenzophenone, 2-hydroxy-4-methoxy benzophenone,2-hydroxy-4-methoxy-4′-methyl benzophenone, 2-hydroxy-4-methoxybenzophenone-5-sulfonate, 4-phenyl benzophenone,2-ethylhexyl-4′-phenyl-benzophenone-2-carboxylate and2-hydroxy-4-n-octoxy benzophenone; 3-(4′-methylbenzylidene)-d,l-camphor,3-benzylidene-d,l-camphor, urocanic acid, urocanic acid ethyl esther,2-phenyl-5-methybenzoxazol, 2,2′-hydroxy-5-methylphenylbenzotriazole,2-(2′-hydroxy-5′-t-octylphenyl)benzotriazole,2-(2′-hydroxy-5′-methylphenyl)benzotriazole, dibenzalazine, dianisoylmethane, 4-methoxy-4′-t-butyldibenzoylmethane, rutin, hesperidine,quercetin, or derivatives thereof including saccharide derivatives. Theamount of the substances is not specifically restricted as long as thesaccharide derivatives of α,α-trehalose are capable of enhancing theeffect of the above substances having UV-absorbing effect alone or incombination with other ingredient. It is usually 0.0001-40%, preferably0.01-20% to total amount of the external dermatological formulation. Inthe case of less than 0.0001%, they are expected to exert the desiredeffect. In the case of more than 40%, they are not dose-dependentlyeffective.

The term “substances having UV-scattering effect “as referred to as inthe present invention include titanium oxide, zinc oxide, seleniumoxide, zirconium oxide; iron oxide, or clay minerals such as kaolin,talc, mica and sericite. The amount of the substances is notspecifically restricted as long as the saccharide derivatives ofα,α-trehalose are capable of enhancing the effect of the abovesubstances having UV-scattering effect alone or in combination withother ingredients. It is usually 0.0001-40%, preferably 0.01-20% tototal amount of the external dermatological formulation. In the case ofless than 0.0001%, they are expected to exert the desired effect. In thecase of more than 40%, they are not dose-dependently effective.

The term “substances having emulsifying effect” as referred to as in thepresent invention includes any one or more non-ionic surfactants and/orionic surfactants. Example of non-ionic surfactants are sorbitan fattyacid esthers such as sorbitan monolaurate and sorbitansesquiisostearate; glycerin fatty acid esthers such as glycerinmonooleate and glycerin monoisostearate; polyglycerin fatty acid estherssuch as diglyceryl monooleate and decaglyceryl diisostearate;polyoxyethylene sorbitan fatty acid esthers such as polyoxyethylenesorbitan monooleate (6 E.O.) and polyoxyethylene sorbitan monooleate (20E.O.); polyoxyethylene sorbit fatty acid esthers such as polyoxyethylenesorbit monolaurate (6 E.O.) and polyoxyethylene sorbit tetraoleate (40E.O.); polyoxyethylene glycerin fatty acid esthers such aspolyoxyethylene glyceryl monooleate (5 E.O.) and polyoxyethyleneglyceryl monooleate (15 E.O.); polyethylene glycol fatty acid estherssuch as polyoxyethylene monoisostearate (10 E.O.) and polyoxyethylenemonooleate; polyoxyethylene glycol difatty acid esthers such aspolyoxyethylene diisostearate (8 E.O.) and polyoxyethylenediisostearate; polyoxyethylene alkyl ether such as polyoxyethylene oleylether (7 E.O.) and polyoxyethylene oleyl ether (10 E.O.);polyoxyethylene polyoxypropylene alkyl ether such as polyoxyethylene(1)polyoxypropylene(4) alkyl ether; and polyoxyethylene caster oil/wax suchas polyoxyethylene caster oil (20 E.O.) and polyoxyethylene caster wax(40 E.O.). In addition, they include propylene glycol fatty acid esthersor ethylene oxide derivatives, polyether denaturation silicone,trehalose mono-fatty acid esthers, trehalose difatty acid esthers,trehalose derivatives such as saccharide derivatives of trehalose fattyacid esthers, sucrose fatty acid esthers, and saccharide derivativessuch as alkyl glucoside.

The ionic surfactant is divided into anionic, cationic and amphoionicsurfactant. Example of the anionic surfactants are higher fatty acids,alkyl sulfate esthers such as alkyl benzene sulfate and α-olefinsulfate, polyoxyethylene alkyl ether sulfate, acyl N-methyl taurinate,alkyl ether phosphate esther, N-acyl amino acid, alkyl amide phosphate,alkyl ether carbonate, or alkali metal, alkaline earth metal,alkanolamin ion, ammonium ion or basic amino acid salts thereof. Exampleof cationic surfactants are alkyl trimethyl ammonium chloride, dialkyldimethyl ammonium chloride, benzalkonium chloride, and alkyl benzylmethyl ammonium. Example of amphoionic surfactants are betaine typeamphoionic surfactants such as betaine alkyl dimethyl aminoacetate,betaine alkyl amide propyl dimethyl amino acetate and2-alkyl-N-carboxymethyl-N-hydroxyethyl imidazolium betaine; amino acidtype amphoionic surfactants such as imidazoline type amphoionicsurfactants, triethanolamine N-cocoacyl-L-glutamate and potassiumN-cocoacyl-L-glutamate; and non-ionic surfactants such aspolyoxyethylene type surfactants, polyalcohol esther type surfactantsand ethylene oxide/propylene oxide block polymers. The substances havingemulsifying effect also include high polymer type surfactants andsubstances having emulsifying effect such as polyvinyl alcohol, sodiumalginate, starch derivatives, cyclodextrins, anhydrous crystallinemaltose, tragacanth gum, lecithin, saponin, isoflavones andphosphatidylcholine.

Varying the purpose of the external dermatological formulation in thepresent invention, total HLB value of the formulation is preferably6-13. Particularly, when used as cleansing cosmetics, the formulation ishard to be washed out under HLB 6 and is lowered in oil-solubility overHLB 13. Polyoxyethylene diisostearate (10 E.O.) or polyoxyethyleneisostearate (10 E.O.) is preferably used in the present invention. Alkylgroups in the above substances having emulsifying effect have usually8-26 carbon atoms, preferably 8-22, more preferably 12-18.

The amount of the substances is not specifically restricted as long asthe saccharide derivatives of α,α-trehalose are capable of enhancing theeffect of the above substances alone or in combination with otheringredients. It is usually 0.0001-50%, preferably 0.01-40% to totalamount of the external dermatological formulation. The substances arepreferably contained in the formulation as cleansing cosmetics in anamount of 6.0-35%. The formulation is hard to solubilize oilyingredients in the solution containing saccharide derivatives ofα,α-trehalose under 6.0%.

The term “substances having astringent effect” as referred to as in thepresent invention includes any substance as long as it has astringenteffect. Example of the substances are menthol, camphor, alum,chlorohydroxy aluminum, ammonium chloride, allantoin aluminum salt, zincsulfate, metal salts of ammonium sulfate such as aluminum potassiumsulfate, zinc sulfophenate, naringin, naringin derivatives such asglycosyl naringin, organic acid such as tannic acid, citric acid, lacticacid and succinic acid. Further, examples of the substances are plantsor plants ingredients including gambir, Sweet hydrangea leaf, Altheaofficinalis root, aloe, fennel, rose fruit, St. John's wort, Lamiumalbum, orange, sea weed, valerian, Artemisa capillaris, bramble, kiwi,gentian, Geranium thunbergii, Chinese gall nut, maybush, meadowsweet,white birch, crataegi fructus tree, bourtree, juniper, nosebleed, sage,thyme, tea leaf, Potantilla tormentilla, nettle, coltsfoot, grape, hop,horse chestnut, balm mint, cornflower, wormwood, apple, lemon,Astragalus sinicus, rosehip, Lonicera japonica, peony root, horse tail,clematis and ivy. The amount of the substances is not specificallyrestricted as long as the saccharide derivatives of α,α-trehalose arecapable of enhancing the effect of the above substances havingastringent effect alone or in combination with other ingredients. It isusually 0.0003-10%, preferably 0.001-5% to total amount of the externaldermatological formulation.

The term “substances having wrinkle-reducing effect” as referred to asin the present invention includes any substance as long as it haswrinkle-reducing effect. Examples of the substances are retinoids suchas retinol, retinoic acid and retinal, pangamic acid, kinetin, ursolicacid, turmeric extract, sphingosine derivatives, silicon, silica,N-methyl-L-serine and mevalonolactone. The amount of the substances isnot specifically restricted as long as the saccharide derivatives ofα,α-trehalose are capable of enhancing the effect of the abovesubstances having wrinkle-reducing effect alone or in combination withother ingredients. It is usually 0.0003-10%, preferably 0.01-5% to totalamount of the external dermatological formulation.

The term “substances having cell-activating effect” as referred to as inthe present invention includes any substance as long as it hascell-activating effect. Example of the substances are amino acids suchas γ-aminobutyric acid and ε-aminocaporonic acid, vitamins such asretinol, thiamine, riboflavin, pyridoxine chloride and pantothenicacids, α-hydroxy acids such as glycolic acids and lactic acid, tannin,flavonoids, saponin, allantoin Kanko-so No. 301 and plant components of“gagome” oarweed, rockweed, Undaria pinnatifida, Lessoniaceae,Nemacystus decipiens or Pterocladia capillacea. The amount of thesubstances not specifically restricted as long as the saccharidederivatives of α,α-trehalose are capable of enhancing the effect of theabove substances having cell-activating effect alone or in combinationwith other ingredients. It is usually 0.0003-10%, preferably 0.001-5% tototal amount of the external dermatological formulation.

The term “substances having transdermal absorption-promoting effect” asreferred to as in the present invention includes any substance as longas it has transdermal absorption-promoting effect. Example of thesubstances are urea, lactic acid, fruit acids, α-hydroxy acids such asglycolic acid, sulfur, β-hydroxy acids such as salicylic acid, oleicacid, undecanoinic acid, octanol, nonanol, menthol, thymol, limonene,dimethylsulfoxide (DMSO), dodecyl methyl sulfoxide, dimethyl lacetamide,N,N-dimethyl formamide, sodium rauryl sulfate, N,N-bis(2hydroxyethyl)oleylamine, polyoxyethlene (20) sorbitan monooleate, dodecyldimethyl ammoniopropanesulfate, propylene glycol, polyethylene glycol,n,n-dimethyl-m-toluamide, DEET (diethyl-m-toluamide), laurocapram,cyclodextrin, 1-dodecylazacycloheptane-2-on, isopropyl myristate,isopropyl palmitate, N-(mono or di)-p-mentane-3-carboxyamide,2-(2-methoxy-1-methylethyl)-5-methylcyclohexanol or azacycloalkanederivatives. The above substances can be used in combination. The amountof the substances is not specifically restricted as long as thesaccharide derivatives of α,α-trehalose are capable of enhancing theeffect of the above substances having cell-activating effect alone or incombination with other ingredients. It is usually 0.0003-20%, preferably0.001-10%, more preferably 0.01-5% to total amount of the externaldermatological formulation. The external dermatological formulation ofthe present invention can be optionally promoted to penetrate into skinsby a delivery system for effective ingredients using liposomes and/or byiontophoresis devices disclosed by the present applicant in Japan PatentPublication Nos. 345,977/02 and 105,515/04. These methods can be used incombination with one or more the above substances having transdermalabsorption-promoting effect.

The formulation of the present invention optionally comprises otheringredients for usual external dermatological formulation. Example ofthe ingredients are powders, oils, fats, edetic acid, di-, tri- ortetrasodium edetate, sodium citrate, oxycarbonic acids or alkaline metalsalts thereof such as lactic acid and sodium lactate, chelating agentssuch as ethylenediamine tetra acetate or alkaline metal salts oralkaline earth metal salts thereof and sodium metaphosphate,antioxidants such as butylhydroxy toluene (BHT), butylhydroxy anisol(BHA) and propyl gallate, water, alcohols such as ethanol andisopropanol, oily substances such as liquid paraffin, vaseline,microcrystalline wax, squalane, ceramide, sweet almond oil, olive oil,hardened oil, caster oil, Japan wax, coconut oil, bees was, lanolin,carnauba wax and palm oil, sterols such as phytosterol, fatty acids suchas lanolic acid, myristic acid, palmitic acid, stearic acid, isostearicacid and oleic acid, or triglyceride thereof, higher alcohols such asrauryl alcohol, cetanol, stearyl alcohol, oleyl alcohol and cholesterol,esthers such as isopropyl myristate, myristyl myristate and isopropylpalmitate, other inorganic or organic acids including α-hydroxy acids oracetic acid such as phosphoric acid, citric acid, malic acid, tartaricacid, lactic acid and succinic acid, or salts thereof, inorganic ororganic alkaline agent such as sodium hydrate, potassium hydrate andtriethanolamine, or salts thereof, fullerene or derivatives thereof,colorants such as yellow iron oxide, titan yellow and carthamin,vitamins such as thiamine, nicotinamide, riboflavin, L-ascorbic acid,pyrrolo-quinoline quinone, carotenoide, ergosterol and tocopherol,naringin, glycosyl naringin, photosensitizing dyes such as Kanko-so No.101 (platonin), Kanko-so No. 301 (takanal), Kanko-so No. 401 andplarumin, tar colorants such as Red No. 104, Yellow No. 4, Yellow No. 5,Green No. 3, Blue No. 1, Blue No. 2, Red No. 202, Red No. 226, Red No.227, Red No. 230, Orange No. 206, Orange No. 207, Yellow No. 202, GreenNo. 201, Green No. 204, Blue No. 201 and Green No. 205, synthetic lakecolorants from carminic acid, laccaic acid, carthamin, brazilin andcrocin, natural colorants such as anthraquinone, anthocyanin andcarotenoid dyes including carthamus colour, gardenia colour,lithospermum root colour, cochineal colour, turmeric colour, monascuscolour, beet colour, lac colour, madder colour, perilla colour, redcabbage colour, red radish colour, elderberry colour, blueberry colour,paprika colour, annatto colour, spirulina colour, cacao colour, tamarindcolour, Japanese persimmon colour, kaoliang colour and caramel colour,ingredients used in bath salts such as sulfur, sodium bicarbonate,sodium chloride, mint, mineral spring, sodium carbonate, sinter, borax,Cnidium rhizome, Japanese angelica root and Schizonepetae herba.

The term “powder” as referred to as in the present invention is notspecifically restricted. Examples of the powder are inorganic powdersuch as talc, kaolin, sericite, white mica, synthetic mica, red mica,black mica, lithia mica, vermiculite, magnesium carbonate, calciumcarbonate, diatomite, magnesium silicate, calcium silicate, aluminumsilicate, barium silicate, strontium silicate, metal salts of tungstate,α-iron oxide, iron oxide hydrate, silica and hydroxyapatite; organicpowder such as nylon powder, polyethylene powder, benzoguanamine powder,ethylene tetrafluoride powder, distylenebenzen pinhole polymer powder,polysaccharide powders including microcrystalline cellulose, celluloidpowder, acetylcellulose powder, cellulose powder, starch powder, chitinpowder and chitosan powder, and protein powders including silk powderand scleroprotein powder, inorganic white pigments such as titaniumoxide and zinc oxide; inorganic red pigments such as ironoxide(colcothar) and iron titanate; inorganic yellow pigments such asyellow iron oxide and yellow ocher; inorganic violet pigments such asmango violet and cobalt violet; inorganic green pigments such aschromium oxide, chromium hydride and cobalt titanate; inorganic bluepigments such as ultramarine blue and Prussian blue; pearl pigments suchas titanium oxide-coated mica, titamiun oxide-coated bismuthoxychloride, bismuth oxychloride, titanium oxide-coated talc, fish scaleguanine, colored titanium oxide-coated mica; and metal powder pigmentssuch as aluminum powder and copper powder. In addition, powderedhydrophobes thereof or the above inorganic powders or organic powdersbound with the above synthetic colorants and/or natural colorants can beused. The amount of the substances is not specifically restricted aslong as the saccharide derivatives of α,α-trehalose are capable ofenhancing the effect of the above substances. It is usually 0.0003-95%,preferably 0.01-80%, more preferably 0.01-75% to total amount of theexternal dermatological formulation.

The word “oil and fat” as referred to as in the present invention is notspecifically restricted. Examples of the oil and fat are synthetic oilsor fats such as medium chain triglyceride; plant oils or fats such assoybean oil, rice oil, rape oil, cotton oil, sesame oil, safflower oil,caster oil, olive oil, cacao oil, camellia oil, sunflower seed oil, palmoil, linseed oil, perilla oil, shea oil, sal oil, coconut oil, Japanwax, jojoba oil, grape seed oil and avocado oil; animal oils or fatssuch as mink oil, egg yolk oil, beef tallow, milk fat and lard; waxessuch as bees wax, spermaceti, lanolin, carnauba wax and candelila wax;hydrocarbons such as liquid paraffin, squalene, squalane,microcrystalline wax, ceresin wax, paraffin wax and vaseline; naturaland synthetic fatty acid such as lauric acid, myristic acid, stearicacid, oleic acid, isostearic acid and behenic acid; natural andsynthetic higher alcohols such as cetanol, stearyl alcohol, hexyldecanol, octyl decanol and rauryl alcohol; esthers or ethers such asisopropyl myristate, isopropyl palmitate, octyldodecyl myristate andcholesterol oleate; and silicone oil.

When containing gums such as carboxyvinylpolymer oracrylate/metaacrylate co-polymer and substances having inhibitory effecton the gel-formation such as ascorbic acid 2-glucoside, the externaldermatological formulation of the present invention can be produced in amanner of adding polyethylene glycol and dipropylene glycol togetherwith the gums and adjusting to pH 5.5-7.5, preferably pH 5.9-7.0, to bea gel form having a high viscosity, satisfactory out looking, andtransparency. The above gel has satisfactory skin feeling withoutoccurring kink or dirt characteristic to cosmetics containingwater-insoluble high polymer such as 1,3-butylene glycol and1,2-pentanediol. The amounts of polyethylene glycol and dipropyleneglycol are not specifically restricted as long as the formulation isformed into a gel having a high viscosity, satisfactory transparency andskin feeling. The amount of polyethylene glycol is usually 0.05-20%,preferably 0.5-5% to total amount of the formulation. The amount ofdibutylene glycol is usually 0.05-20%, preferably 0.5-5% to total amountof the formulation.

The amount of gums such as carboxyvinylpolymer and polyacrylate polymerare not specifically restricted as long as the formulation is formedinto a gel having a high viscosity, satisfactory transparency and skinfeeling. It is usually 0.05-15%, preferably 0.5-10%, more preferably0.5-2% to total amount of the formulation.

The external dermatological formulation of the present invention cancontain the substances having water-solubilizing effect for the purposeof stabilizing aqueous substances such as ascorbic acid. Examples ofsuch substances having water-solubilizing effect are lower alcohols,higher alcohols such as glycerin, ethylene glycol and propylene glycol,hydrogenated soybean phospholipids, polyoxyethylene sorbitan fatty acidesthers, polyoxyethylene lanolin alcohols, polyoxyethylene caster oil,polyoxyethylene caster wax, polyoxyethylene sterol, polyoxyethylenealkyl ethers, polyoxyethylene, polyoxypropylene alkyl ethers orpolyoxyethylene alkyl phenyl ethers. Preferable examples are ethanol,glycerin, ethylene glycol, propylene glycol, 1,3-butylene glycol,diethylene glycol, dipropylene glycol, hydrogenated soybeanphospholipids, polyoxyethylene sorbitan fatty acid esthers,polyoxyethylene lanolin alcohols, polyoxyethylene caster oil,polyoxyethylene caster wax or polyoxyethylene alkyl ethers.

When produced with carbomer type of acrylic polymer or gums mixturecontaining isoparaffin, polyacrylamide and polyoxyethylene raurylalcohol as main ingredients, as gums or stabilizers, the formulation ofthe present invention preferably contains 1-8% on a dry solid basis ofsaccharide derivatives of α,α-trehalose to a final weight in the mannerof adding the saccharide derivatives or a saccharide mixture containingthe same to the gums mixture until swelling with water. As result, theformulation is easily emulsified due to the improvement ofwater-solubility of the gums mixture, and efficiently produced. In orderto improve skin feeling, 1,3-butylene glycol is optionally added to theformulation in an amount of 0.5-3.0% to the final product together withsaccharide derivatives of α,α-trehalose.

The external dermatological formulation can comprise one or more membersselected from the group consisting of lymphokines such as interferon-α,interferon-β, interferon-γ, tumor necrosis factor-α, tumor necrosisfactor-β, macrophage migration inhibitory factor, colony stimulatingfactor, transfer factor, interleukin-2; hormones such as insulin growthhormone, prolactin, erythropoietin, follicle stimulating hormone andsteroids; antibiotics such as penicillin, erythromycin, chloramphenicol,tetracycline, streptomycin and kanamycin sulfate; enzymes such aslipase, elastase, urokinase, protease, β-amylase, isoamylase, glucanaseand lactase; ginseng; aloe; mallow; iris; grape seed; coix seed; balmmint; nosebleed; loofah; lily; phellodendron bark; peony root; sialid;birch; loquat; chlorella; propolis extract; fungus such as redcurrants,Ganoderma lucidum, deer horn shape Ganoderma lucidum and Phellinuslinteus; plant extract such as herbs; animal extracts such as snappingturtle extract; seaweed extract such as Enteromorpha compressa extractand yellow green layer extract; royal jelly; galenicals; high intensitysweeteners such as dihydrochalcone, stevioside, α-glycosyl stevioside,rebaudioside, glycyrrhizin, L-aspartyl-L-phenylalanine methyl esther,acesulfame-K and sucralose, saccharin; minerals or compounds thereofsuch as calcium, magnesium, iron, manganese, cobalt, copper, zinc,phosphorus, selenium, fluorine and iodine; alkaline ionized water;acidic ionized water; and magnetized water.

If necessary, the external dermatological formulation can also compriseone or more substances used for pharmaceuticals, quasi-drugs, cosmeticsor toiletries, described in “Japanese Standard of Cosmetic Ingredients”,“Supplement to the Japanese of Cosmetic Ingredients codex”, “JapaneseCosmetic Ingredients Codex by Category”, “Japanese Quasi-drugIngredients Codex”, “The Japanese Pharmacopoeia”, Supplement to theJapanese Pharmacopoeia codex”, Japanese Standards of PharmaceuticalAdditive”, “Japanese Standards of Herbal Medicine”, “The JapaneseStandards of Food Additives”, “Latest Cosmetic Science (Saishin KeshohinKagaku), revised and enlarged edition II”, published by The Yakuji NippoLtd, in Jul. 10, 1992, “New Cosmetology (Shin Keshohingaku)”, publishedby Nanzando Co. Ltd., in Jan. 18, 2002, or “Cosmetic and ToiletryFormulation, 2nd edition”, Vol. 8, published by William AndrewPublisher, in 2001. Examples of such ingredients are pharmaceuticals,excipients, bases, emollients, cooling agents, astringents,refrigeratives, surfactants, emulsifiers, dispersing agents,solubilizing agents, solvents, alkaline chemicals, thickening agents,gums, film-forming agents, foaming agents, antifoaming agents,perfumeries, coloring agents, stabilizers, antiseptics, bactericides,discoloration inhibitory agents, antioxidants, hair treating agents,humectants, hair-protecting agents, tricks activator agents,antielectrostatic agents, solvents, solubilizing agents, plasticizers,suspending agents, buffering agents, sweeteners, refrigeratives,sweetening agents, binders, absorbents, propellants, coating agents,masticatories, fillers, softeners, adjusters, chelating agents,discoloration inhibitory agents, oils, fats, oil-soluble polymer,inorganic or organic pigments, inorganic or organic pigments treatedwith silicone or fluoro compounds, pigments such as organic dyes,photosensitizing dyes such as rumin, waxes, antiperspirants, deodorants,anti-wrinkle agents, sebum secretion inhibitors, antiseborrheic agents,parakeratosis inhibitors, horny layer removers, horny layer resolvingagents, analgestics, torpents, antiplasmic agents, nutritionalsupplements, antiandrogenic agents, antihistamic agents,phosphodiesterase inhibitors, adipose cell differentiation inhibitoryagents, lipase inhibitors, collagenase inhibitors, tyrosinaseinhibitors, fibroblast activating agents, and collagen-productionpromoting agents. If necessary, food ingredients can be used. The aboveingredients can be used in any amount for the external dermatologicalformulation of the present invention as long as they do not affect thedesired effects.

Any form of the formulation can be used; for example, solution form,emulsion form, powder-dispersion form, water-oil form, water-powder formor water-oil-powder form. The formulation of the present invention canbe used as base cosmetics, finishing cosmetics, skin cosmetics,cleansing cosmetics, face washes, skin lotions, creams, milky lotions,packs, foundations, face powders, powders, rouges, eyebrow, eye andcheek care cosmetics, perfume, bath cosmetics, oral care cosmetics,tanning cosmetics, sun care cosmetics, makeup cosmetics, nail cosmetics,eye liner cosmetics, mouth and lip care cosmetics, oral care cosmetics,facial care cosmetics, cosmetic oils, fragrant cosmetics, body carecosmetics, hair care cosmetics, hair wash cosmetics, cosmetic soaps,medicated soaps, toothpaste, oral refrigeratives, hircismus blockers,bath dusting powders, hair growth promoters, tonics, shaving cosmetics,sunscreens, antiiching agents, wiping and cleaning agents, bactericide,disinfectant, decolorants and depilatories, further, preventing ortreating agent for athlete's foot, hemorrhoids, acnes, wounds, burns,chilblains, rashes, festers, inflammations, infections, allergies,atopic diseases, ulcers or tumors in the form of a skin lotion, lotion,milky lotion, cream, ointment, plaster, suspension, emulsion, paste,mousse, tic, solid, semisolid, powder, solid powder, mid-containerforming powder, block, pencil, stick, jelly, gel, aerosol, spray,lozenge, pack or facemask. Example of such cosmetics are cosmetic soaps,face cleansing creams, cleansing foams, cleansing milks, cleansinglotions, cleansing oils, massage creams, cold creams, moisture creams,vanishing creams, hand creams, moisture lotions, cosmetic oils, liquidfoundations, powder foundations, cake foundations, stick foundations,oily compact foundations, creamy foundations, cheek blushers, emulsifiedfoundations, foundation cosmetics, body powders, creamy face powders,face powders, liquid face powders, solid face powders, talcum powders,wet face powders, loose shadows, baby powders, cheek colors, pencils,mascaras, lipsticks, lip creams, packs, shaving creams, after shavingcreams, lotions, hand lotions, shaving lotions, after shaving lotions,sun screen creams, tanning oils, sun screen lotions, tanning lotions,softening skin lotions, astringent skin lotions, cleansing skin lotions,multi-layer skin lotions, facial shampoos, body shampoos, hair shampoos,hair-washing powders, hand soaps, facial rinses, body rinses, hairrinses, hair treatments, pilatories, tonics, tics, pomades, hair creams,hair liquids, hair tonics, set lotions, combing oils, combing oils forside hair, hair sprays, hair mousses, hair tonics, hair dyes, hairbleachers, color rinses, color sprays, permanent wave liquids, presspowders, loose powders, eye creams, eye shadows, cream eye shadows,powder eye shadows, eye liners, eye blow pencils, mascaras, depilatorycreams, perfumes, kneaded perfumes, powder perfumes, eau de cologne,deodorants, bath preparations, bath oils, bath salts, cosmetic oils,baby oils, nail colors, enamels, enamel removers, nail treatments, mouthwashes, toothpastes, tooth powders, insect repellers, ointments fortreating wounds, antibacterial creams, steroid ointments, and further,cataplasms in the form of sheet or film, laundry soaps or detergents forclothes, detergents for flower, detergents for kitchen and cleansers.

The saccharide derivatives of α,α-trehalose used in the presentinvention are stable even in the strong acidic or alkaline condition.Therefore, the external dermatological formulation of the presentinvention can be adjusted to any pH suitable for use thereof. The pH isusually 3-12. When the formulation is a cream or skin lotion, it ispreferably adjusted to pH4-12, and more preferable pH5-9 nearer toskin's pH. When the formulation is a cleansing us such as soaps orshampoos, it is usually adjusted to a neutral and alkaline side, andpossibly to round pH 13. When the formulation is a soap, the saccharidederivatives of α,α-trehalose prevent the formulation to be cloudy andyellowish, and enable to produce a transparent soap. The formulation ofthe present invention can be adjusted to any osmotic pressure. If it isa skin lotion having a higher water-content, it is preferably adjustedto osmotic pressure of 200-600 mOsm in order to be lowered in thestimulation to skins.

The following experiments explain the external dermatologicalformulation according to the present invention in detail.

Experiment 1:

Influence of Saccharide Derivatives of α,α-trehalose on Substanceshaving Antiinflammatory Effect

To confirm the influence of saccharide derivatives of α,α-trehaloseand/or glycyrrhizinic acid on the burned skins due to the inflammationafter sunbath, the following experiment was carried out. Skin lotionscontaining glycyrrhizinic acid, which is used generally as a cosmeticingredient having an effect on inhibiting the inflammation of skins dueto sunburn, and α-glucosyl α,α-trehalose or α-maltosyl α,α-trehalose,which is a kind of saccharide derivatives of α,α-trehalose, wereprepared for the following experiment to confirm the influence on theburn of skins after sun bath. As shown in Table 1, skin lotion(formulation No. 1) was prepared by admixing a base preparationconsisting of 3.0 parts by weight of ethanol, 10.0 parts by weight of1,3-butylene glycol, 0.5 part by weight of polyoxyethylene(15)oleylalcohol ether, 0.1 part by weight of oleylalcohol, 0.1 part byweight of ethyl paraben and 0.02 part by weight of perfumery with anappropriate amount of purified water to give a final weight of 100 partsby weight. Skin lotions (formulation Nos. 2-4) were prepared by addingeither of 0.5 part by weight on a dry solid basis of hydrous crystallineα-glucosyl α,α-trehalose (purity 99.0% or more) prepared according toExperiment B-1 of Japanese Patent Publication (Kokai) No. 291,986/95,0.5 part by weight on a dry solid basis of a powdery α-maltosylα,α-trehalose (purity 98.1%) prepared according to the following Example5, or 0.5 part by weight of glycyrrhizinic acid to the base preparationand admixed with an appropriate amount of purified water to give a finalweight of 100 parts by weight. Skin lotions (formulation Nos. 8-10) wereprepared by adding 0.5, 1.5 or 5.0 parts by weight, on a dry solid basisof the powdery α-maltosyl α,α-trehalose (purity 98.1%) and 0.5 part byweight of glycyrrhizinic acid to the base preparation, and admixing withan appropriate amount of purified water to give a final weight of 100parts by weight.

Method of Test

Thirteen panels (women aged 20s and 30s) were asked to use the skinlotions (formulation Nos. 1-10) for two days in a prescribed mannerafter enjoying a sea bathing in a summer beach for a half day. Then,they were asked the questionnaires; satisfaction with theantiinflammatory effect (effect on suppressing the burn of the skins intheir backs, shoulders and outside of upper parts of their arms), andthe skin feeling in terms of sticky feeling and refreshness. Table 1shows the numbers of panels who were satisfied with the effect for eachskin lotion, and the percentages thereof (%). Table 1 also shows thenumbers of panels satisfied with the skin feeling without sticky feelingin the skins for each skin lotion and the percentages thereof (%) TABLE1 Amount (part by weight) Ingredient No. 1 No. 2 No. 3 No. 4 No. 5 No. 6No. 7 No. 8 No. 9 No. 10 Glycyrrhizinic acid 0.0 0.0 0.0 0.5 0.5 0.5 0.50.5 0.5 0.5 α-Glucosyl α,α-trehalose 0.0 0.5 0.0 0.0 0.5 1.5 5.0 0.0 0.00.0 (dry solid basis) α-Maltosyl α,α-trehalose 0.0 0.0 0.5 0.0 0.0 0.00.0 0.5 1.5 5.0 (dry solid basis) Base Ethanol 3.0 3.0 3.0 3.0 3.0 3.03.0 3.0 3.0 3.0 ingredient 1,3-Butyleneglycol 10.0 10.0 10.0 10.0 10.010.0 10.0 10.0 10.0 10.0 Polyoxyethylene(15) 0.5 0.5 0.5 0.5 0.5 0.5 0.50.5 0.5 0.5 oleylalcoholether Oleylalcohol 0.1 0.1 0.1 0.1 0.1 0.1 0.10.1 0.1 0.1 Ethylparaven 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1Perfumeries 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 0.0 Purified waterremain- remain- remain- remain- remain- remain- remain- remain- remain-remain- der der der der der der der der der der Total 100.0 100.0 100.0100.0 100.0 100.0 100.0 100.0 100.0 100.0 Judgement Panels satisfied 0 11 4 8 13 13 9 13 13 with the effect on  (0)  (8)  (8) (31) (62) (100)(100) (69) (100) (100) suppressing burn Panels satisfied 5 13 13 4 8 1113 9 13 13 with the effect on (38) (100) (100) (31) (62)  (85) (100)(69) (100) (100) skin feeling

As evident from the result in Table 1, the skin lotions; formulation No.2 containing 0.5 part by weight of α-glucosyl α,α-trehalose(concentration of 0.5%), and formulation No. 3 containing 0.5 part byweight of α-maltosyl α,α-trehalose (concentration of 0.5%), were judgedto have satisfactory effect on suppressing the burn by only 8% ofpanels. The skin lotion; formulation No. 4 containing 0.5 part by weightof glycyrrhizinic acid (concentration of 0.5%) was judged to havesatisfactory effect on suppressing the burn by about 31% of panels.Among the skin lotions containing 0.5 part by weight of glycyrrhizinicacid, formulation No. 5 containing 0.5 part by weight of α-glucosylα,α-trehalose (concentration of 0.5%, on a dry solid basis), andformulation No. 8 containing 0.5 part by weight of α-maltosylα,α-trehalose (concentration of 0.5%, on a dry solid basis), were judgedto have satisfactory effect on suppressing the burn by 62% and 69% ofpanels, respectively. Further, among the skin lotions containing 0.5part by weight of glycyrrhizinic acid (concentration of 5%, on a drysolid basis), the skin lotions containing 1.5 parts by weight ofα-glucosyl α,α-trehalose (concentration of 1.5%, on a dry solid basis:formulation No. 6), 5.0 parts by weight of α-glucosyl α,α-trehalose(concentration of 5.0%, on a dry solid basis: formulation No. 7), 1.5parts by weight of α-maltosyl α,α-trehalose (concentration of 1.5%, on adry solid basis: formulation No. 9), and 5.0 parts by weight ofα-maltosyl α,α-trehalose (concentration of 5.0%, on a dry solid basis:formulation No. 10) were judged to have satisfactory effect onsuppressing the by all panels. These results reveal that α-glucosylα,α-trehalose or α-maltosyl α,α-trehalose, which is a kind of saccharidederivatives of α,α-trehalose, is capable of enhancing theantiinflammatory effect of glycyrrhizinic acid in a dose dependentmanner.

As regards the skin feeling, skin lotion containing only baseingredients without α-glucosyl α,α-trehalose or α-maltosyl α,α-trehalose(formulation No. 1), was judged to have satisfactory skin feeling by 38%of panels. In contrast, skin lotions containing 0.5 part by weight ofα-glucosyl α,α-trehalose (concentration of 0.5%, on a dry solid basis:formulation No. 2), and containing 0.5 part by weight of α-maltosylα,α-trehalose (concentration of 0.5%, on a dry solid basis: formulationNo. 3) were judged to have satisfactory skin feeling by all panels.Further, skin lotion, containing 0.5 part by weight of glycyrrhizinicacid (concentration of 0.5%, on a dry solid basis: formulation No. 4) to100 parts by weight of the skin lotion together with only baseingredients, was judged to have satisfactory skin feeling by 31% ofpanels. In contrast, the skin lotions, further containing 0.5 part byweight of α-glucosyl α,α-trehalose (concentration of 5%, on a dry solidbasis: formulation No. 5) and 0.5 part by weight of α-maltosylα,α-trehalose (concentration of 5%, on a dry solid basis: formulationNo. 8), were judged to have satisfactory skin feeling by 62% and 69% ofpanels, respectively. Furthermore, skin lotions, containing 1.5 parts byweight of α-glucosyl α,α-trehalose (concentration of 1.5%, on a drysolid basis: formulation No. 6), 1.5 parts by weight of α-maltosylα,α-trehalose (concentration of 1.5%, on a dry solid basis: formulationNo. 9), on a dry solid basis, together with 0.5% of glycyrrhizinic acidto 100 parts by weight of the skin lotion (concentration of 0.5%, on adry solid basis) and base ingredients, were judged to have satisfactoryskin feeling by 85% and 100% of panels, respectively. In addition, theskin lotions, further containing 5 parts by weight of α-glucosylα,α-trehalose (concentration of 5.0%, on a dry solid basis: formulationNo. 7) and α-maltosyl α,α-trehalose (formulation No. 10) were judged tohave satisfactory effect by all panels. These results reveal thatα-glucosyl α,α-trehalose or α-maltosyl α,α-trehalose has the effects onsuppressing sticky feeling of the skin lotion containing only baseingredients or containing base ingredients and glycyrrhizinic acid toimprove skin feeling.

Experiment 2:

Influence of Saccharide Derivatives of α,α-Trehalose on SubstancesHaving Blood Flow-Promoting Effect

Fallen hair and itch of the head skins are sometimes caused by aninsufficient blood flow. To confirm the influence of saccharidederivatives of α,α-trehalose and/or substances having bloodflow-promoting effect on the blood flow of head skins, the followingexperiment was carried out.

Preparation of Saccharide Derivatives of α,α-Trehalose

The syrup containing saccharide derivatives of α,α-trehalose, preparedin Example 1, was hydrogenated according to Example 6 to convertreducing saccharides in the syrup into corresponding sugar alcohols.After separated from Raney nickel, the resulting solution was decolored,desalted, and concentrated to obtain a syrup. The syrup, containing 0.8%of α-glucosyl α,α-trehalose, 52.8% of α-maltosyl α,α-trehalose, 1.3% ofα-maltotriosyl α,α-trehalose, 7.7% of other saccharide derivatives ofα,α-trehalose, 1.9% of sorbitol, 8.0% of maltitol, 10.7% ofmaltotriitol, 16.6% of maltotetraitol, and 0.2% of other sugar alcohols,had a concentration of 75%.

Preparation of Hair Tonics as Test Samples

As shown in Table 2, 4.6 parts by weight of the above syrup containingsaccharide derivatives of α,α-trehalose (2.0 parts by weight ofsaccharide derivatives of α,α-trehalose, on a dry solid basis), wereadmixed with two or three substances having blood flow-promoting effectselected from 1.0 part by weight of sialid extract, 1.0 part by weightof ginseng extract and 0.5 part by weight of α-dl-tocopherol, andfurther admixed with 60.0 parts by weight of ethylalcohol, 2.0 parts byweight of propylene glycol, and up to 100 parts by weight of water toprepare hair tonics (Formulation Nos. 1-4). 4.6 parts by weight of thesame syrup prepared in Example 1 was admixed with any one of one part byweight of sialid extract, 1.0 part by weight of ginseng extract and 1.0part by weight of α-dl-tocopherol, and further admixed with 60.0 partsby weight of ethylalcohol, 2.0 parts by weight of propylene glycol, andup to 100 parts by weight of water to prepare hair tonics (formulationNos. 5-8).

Method of Test

Eleven panels (males aged 40s and 50s), having itch of their head skinsdue to insufficient blood flow, were asked to use the hair tonics(formulation Nos. 1-8) for 14 days in a manner of spreading anappropriate amount of each hair tonic over their head skins two times aday. Then, they were asked the questionnaires; suppressing effectagainst fallen hair or itch of head skins. The hair tonics were comparedwith each other in view of the skin feeling including sticky feeling andrefreshing feeling after use. Table 2 shows the numbers of panels weresatisfied with the suppressing effect of each hair tonic on fallen hairand itch of head skin, and the percentages thereof (%). Table 2 alsoshows the numbers of panels satisfied the skin feeling without stickyfeeling against skins of each skin lotion and the percentages thereof(%). TABLE 2 Amount (part by weight) Ingredient No. 1 No. 2 No. 3 No. 4No. 5 No. 6 No. 7 No. 8 Saccharide 2.0 2.0 2.0 2.0 2.0 0.0 0.0 0.0derivatives of α,α-trehalose (Dry solid basis) Ethanol 60.0 60.0 60.060.0 60.0 60.0 60.0 60.0 Sialid extract 1.0 1.0 0.0 1.0 0.0 1.0 0.0 0.0Ginseng extract 0.0 1.0 1.0 1.0 0.0 0.0 1.0 0.0 α-dl-Tocopherol 0.5 0.00.5 0.5 0.0 0.0 0.0 0.5 Propylene glycol 2.0 2.0 2.0 2.0 2.0 2.0 2.0 2.0Purified water Remain- Remain- Remain- Remain- Remain- Remain- Remain-Remain- der der der der der der der der Total 100.0 100.0 100.0 100.0100.0 100.0 100.0 100.0 Judgement Panels satisfied 10 10 10 10 1 3 3 4with the effect on (91) (91) (91) (91)  (9) (27) (27) (36) suppressingfallen hair (%) Panels satisfied 8 9 8 10 2 3 4 3 with the effect on(73) (82) (73) (91) (18) (27) (36) (27) suppressing itch (%) Panelssatisfied 11 11 11 11 11 5 6 4 with the effect on (100)  (100)  (100) (100)  (100)  (45) (55) (36) skin feeling (%)

As evidence from the result in Table 2, hair tonic containing only 2.0parts on a dry solid basis by weight of saccharide derivatives ofα,α-trehalose to 100 parts be weight of hair tonic together with ethanoland propylene glycol, (concentration of 2.0%: Formulation No. 5) was notjudged to have a satisfactory effect on suppressing itch of head skinsor fallen hair. Hair tonic containing only 1.0 part by weight of sialidextract (concentration of 1.0%: Formulation No. 6), 1.0 part by weightof ginseng extract (concentration of 1.0%: formulation No. 7), or 0.5part by weight of α-dl-tocopherol (concentration of 1.0%: formulationNo. 8) to 100 parts by weight of hair tonic together with ethanol andpropylene glycol were judged to have a satisfactory effect onsuppressing fallen hair by 27%, 27% and 36% of panels, respectively, anditch of head skins by 27%, 36% and 27% of panels, respectively. Incontrast, hair tonics containing two parts by weight of saccharidederivatives of α,α-trehalose (concentration of 2.0%) and two or three of1.0 part by weight of sialid extract (concentration of 1.0%), 1.0 partby weight of ginseng extract (concentration of 1.0%) and 0.5 part byweight of α-dl-tocopherol (concentration of 0.5%) together with ethanoland propylene glycol were judged to have a satisfactory effect on fallenhair by 91% of panels. As regards the effect on suppressing the itch ofhead skin, hair tonic containing two parts on a dry solid basis byweight of saccharide derivatives of α,α-trehalose (concentration of2.0%), 1.0 part by weight of sialid extract (concentration of 1.0%), 0.5part by weight of α-dl-tocopherol (concentration of 0.5%) together withethanol and propylene glycol to 100 parts by weight of hair tonic(formulation No. 1) was judged to have a satisfactory effect by 73% ofpanels; hair tonic containing two parts on a dry solid basis by weightof saccharide derivatives of α,α-trehalose (concentration of 2.0%), 1.0part by weight of sialid extract (concentration of 1.0%), 1.0 part byweight of ginseng extract (concentration of 1.0%: formulation No. 2) wasjudged to have a satisfactory effect by 82% of panels; hair toniccontaining 2 parts on a dry solid basis by weight of saccharidederivatives of α,α-trehalose (concentration of 2.0%), 1.0 part by weightof ginseng extract (concentration of 1.0%), 0.5 part by weight ofα-dl-tocopherol (concentration of 0.5%: formulation No. 3) was judged tohave a satisfactory effect by 73% of panels; hair tonic containing 2parts on a dry solid basis by weight of saccharide derivatives ofα,α-trehalose (concentration of 2.0%), 1.0 part by weight of sialidextract (concentration of 1.0%), 1.0 part by weight of ginseng extract(concentration of 1.0%), 0.5 part by weight of α-dl-tocopherol(concentration of 0.5%: formulation No. 4) was judged to have asatisfactory effect by 91% of panels. These results reveal thatsaccharide derivatives of α,α-trehalose are effective on suppressingfallen hair and itch of head skins in combination with two or three ofsubstances having blood flow-promoting effect such as sialid extract,ginseng extract and α-dl-tocopherol.

As regards to skin feeling, hair tonics without saccharide derivativesof α,α-trehalose (formulation Nos. 6-8) were judged to have satisfactoryeffect on skin feeling by 36-55% of panels. In contrast, hair tonicscontaining 2.0 parts by weight of saccharide derivatives ofα,α-trehalose (concentration of 2.0%: Formulation Nos. 1-5) were judgedto have a satisfactory effect on skin feeling by all of 11 panels withor without substances having blood flow-promoting effect. These resultsreveal that saccharide derivatives of α,α-trehalose are effective onsuppressing sticky feeling and improving skin feeling of hair toniccontaining ethanol, propylene glycol and purified water and hair toniccontaining ethanol, propylene glycol, purified water and substanceshaving blood flow-promoting effect.

Experiment 3:

Influence of Coexisting with Saccharide Derivatives of α,α-Trehalose onEasily Browning Substances Used for Usual External DermatologicalFormulation

Various substances, used for external dermatological formulation,sometime cause of browning (including coloring) in the case ofcombination use with other substances. To confirm the influence ofcombination of L-ascorbic acid, used as a substance havingantiinflammatory effect for external dermatological formulation andknown to cause of browning, and saccharide derivatives of α,α-trehalose,the following experiment was carried out.

Preparation of Test Solution

13.3 parts by weight of the syrup containing saccharide derivatives ofα,α-trehalose (10.0 parts by weight of solid base of saccharides), usedin Experiment 2, and 1.0 part by weight of L-ascorbic acid weredissolved in an appropriate amount of purified water. The resultingsolution was adjusted to about pH 6.5, and admixed with purified waterto prepare 100 parts by weight of an aqueous solution. As a control, anaqueous solution was prepared by dissolving 1.0 part by weight ofL-ascorbic acid in an appropriate amount of purified water, adjusting toabout pH 6.5 and admixing with water to give a final weight of 100parts. An aqueous solution further containing 10 parts by weight ofglycerin (concentrated glycerin in cosmetic grade, commercialized by KaoCo., Ltd., Tokyo, Japan) instead of saccharide derivatives ofα,α-trehalose was prepared.

Method of Test

Three resulting solutions were kept at 50° C. under the shaded conditionfor 14 days. To examine browning, values of absorbance 420 nm of thetest samples were measured by usual method and compared with that of thestarting test samples. To examine the degree of coloring, relativevalues of test samples were calculated by comparing the value ofdifferential absorbance of the solution containing only L-ascorbic acid,defined as 100%. TABLE 3 Absorbance Absorbance of test Difference ofstarting sample kept of Degree of test sample after 14 days absorbancecoloring Ingredient (420 nm) (420 nm) (420 nm) (%) L-Ascorbic 0.0015.000 4.999 100 acid L-Ascorbic 0.001 3.064 3.063 61 acid + GlycerinL-Ascorbic 0.001 1.353 1.352 27 acid + Saccharide derivatives ofα,α-trehalose

As evidence from the result in Table 3, the aqueous solution containingL-ascorbic acid was observed to be a strong browning after two weeks.The aqueous solution containing L-ascorbic acid and saccharidederivatives of α,α-trehalose was lowered to about 27% of the degree ofsolution containing no saccharide derivatives of α,α-trehalose. Theaqueous solution containing L-ascorbic acid and glycerin was lowered toabout 61% of the degree of solution containing no glycerin. Saccharidederivatives of α,α-trehalose more strongly inhibited the browning ofL-ascorbic acid than glycerin did. These results reveal that saccharidederivatives of α,α-trehalose are effective on inhibiting the browning ofL-ascorbic acid. A syrup at the concentration of 75%, containing about53% of α-maltosyl α,α-trehalose and 5% of other saccharide derivativesof α,α-trehalose, on a dry solid basis, as a material of the syrupbefore hydrogenation used in this experiment, was examined in view ofinfluence to browning of L-ascorbic acid according to Experiment 3. As aresult, it is revealed to have almost equal effect to the hydrogenatedsaccharide mixture containing saccharide derivatives of α,α-trehalose,used in Experiment 3, in view of inhibition of the browning ofL-ascorbic acid. The same experiment to the above except to co-existingof 10 mM iron ion was carried out. As a result, saccharide mixturecontaining saccharide derivatives of α,α-trehalose inhibited thebrowning of L-ascorbic acid. Therefore, it is suggested to havechelating activity against iron ion.

Experiment 4:

Influence of Saccharide Derivatives of α,α-Trehalose on MoisturizingSkins

To confirm the influence of saccharide derivatives of α,α-trehalose onmoisturizing skins, the following experiment using hyaluronic acid as apositive control was carried out.

Preparation of Test Skin Lotion

As shown in Table 4, one part by weight of 1,2-pentandiol, one part byweight of 1,3-butylene glycol, two parts by weight of ethanol, one partby weight of “Hyaluronic Acid FCH”, a 1% aqueous hyaluronic acidsolution (molecular weight 1,800,200,000) commercialized by Kibun FoodChemifa Co., Ltd., Tokyo, Japan, and/or 5.2 parts by weight on a drysolid basis of syrup containing saccharide derivatives of α,α-trehalose(3.0 parts by weight on a dry solid basis of saccharide derivatives ofα,α-trehalose), used in Experiment 2, were dissolved in an appropriateamount of purified water. The resulting solution was admixed withpurified water to give a final weight of 100 parts by weight to preparetest skin lotions (formulation Nos. 1-3).

Method of Test

Influence of test skin lotions on the moisture of the skins was judgedby measuring conductance as a reference for hydration level of skin. Atfirst, the conductance of skin surface at the body side of upper rightarm of all panels consisting of 15 males and 15 females were measuredusing “SKICON-200EX”, a skin surface hygrometer commercialized by I.B.SCo., Ltd., Shizuoka, Japan, before using the test skin lotions. Then,panels were randomly divided into three groups consisting of five malesand five females. Panels were applied with one of the skin lotionsformulation Nos. 1-3 listed in Table 4, at the same positions (skinsurface at the body side of upper right arm) pre-measured above. Afterair drying for five minutes, the conductance at the positions wasmeasured using the skin surface hygrometer. Table 4 shows the averagesof 10 panels of each group. TABLE 4 Formulation No. 1 No. 2 No. 31,2-Pentanediol 1.0 1.0 1.0 1,3-Butylene glycol 1.0 1.0 1.0 Ethanol 2.02.0 2.0 Hyaluronic acid 1.0 0.0 1.0 (1% aqueous solution) Syrupcontaining 0.0 5.2 5.2 saccharide derivatives of α,α-trehalose (Drysolid basis) Purified water Appropriate Appropriate Appropriate amountamount amount Total amount 100 100 100 Moisture content Before 43 41 40(μS) After 52 (121) 75 (183) 84 (210) (Relative value)

As evidence from the result in Table 4, the average of conductancehaving a relation with moisture content of skin surface before applyingthe skin lotion was about 40-43 micro Siemens (μS), and the average ofconductance after applying the skin lotion containing 0.01% ofhyaluronic acid to total weight was 52 μS meaning 21% increase ascompared with that of before applying. In contrast, the average ofconductance after applying the skin lotion containing 5.2% on a drysolid basis of the syrup containing saccharide derivatives ofα,α-trehalose was 83% increase as compared with that of before applying.Further, the average after applying the skin lotion containing 0.01% ofhyaluronic acid and 5.2% of the syrup containing saccharide derivativesof α,α-trehalose was 84 μS meaning 110% increase as compared with thatof before applying. These results reveal that saccharide derivatives ofα,α-trehalose imparts the moisturizing effect to skins and has asatisfactory effect as a moisturizing agent for external dermatologicalformulations, and the moisturizing effect of the saccharide derivativesof α,α-trehalose is further enhanced in combination with hyaluronicacid. In addition, as regards skin feeling after applying the test skinlotion, all panels judged that the skin lotion containing saccharidederivatives of α,α-trehalose had less sticky feeling and moresatisfactory skin feeling than that of only hyaluronic acid. All panelsalso judged that the skin lotion containing both of hyaluronic acid andthe syrup containing saccharide derivatives of α,α-trehalose had moresatisfactory skin feeling than that of single use thereof.

The following examples explain the present invention. The followingexamples explain saccharide material containing saccharide derivativesof α,α-trehalose and process thereof, and its use for externaldermatological formulations. The present invention is not restricted toonly these examples.

EXAMPLE 1

A corn starch was prepared into an about 20% of starch suspension,admixed with calcium carbonate to give a final concentration of 0.1%,and adjusted to pH 6.5. The resulting solution was admixed with0.2%/g-starch on a dry solid basis of “TERMAMYL 60L”, an α-amylasecommercialized by NovoZyme A/S, Bagsvæard, Denmark, and followed by theenzyme reaction at 95° C. for 15 minutes. After autoclaved at 120° C.for 10 minutes, the resulting reaction mixture was cooled to 50° C.,adjusted to pH 5.8, admixed with 5 units/g-starch ofmaltotetraose-forming amylase disclosed in Japanese Patent Publication(Kokai) No. 240,784/88, commercialized by Hayashibara BiochemicalLaboratories Inc., Okayama, Japan, and 500 units/g-starch of isoamylasecommercialized by Hayashibara Biochemical Laboratories Inc., Okayama,Japan, and followed by the enzymatic reaction for 48 hours. The reactionmixture was further admixed with 30 units/g-starch of “α-AMYLASE 2A”,α-amylase commercialized by Ueda Chemical Industries Co., Ltd., Hyogo,Japan and followed by the enzyme reaction at 65° C. for four hours.After autoclaved at 120° C. for 10 minutes, the reaction mixture wascooled to 45° C., admixed with 2 units/g-starch of a non-reducingsaccharide-forming enzyme originated from Arthrobacter sp. Q36 (FREMBP-4316), disclosed in Japanese Patent Publication (Kokai) No.143,876/95, and followed by an enzymatic reaction for 48 hours. Thereaction mixture was kept at 95° C. for 10 minute, cooled and filteredto obtain a filtrate. According to conventional manner, the resultingfiltrate was decolored with activated charcoal, desalted and purifiedwith ion exchangers in H- and OH-forms, and concentrated into 70% syrupin a yield of about 90% to the material starch on a dry solid basis. Thesyrup showed DE 13.7 and contained 52.5% of α-maltosyl α,α-trehalose(alias α-maltotriosyl α-glucoside), 4.1% of α-glucosyl α,α-trehalose(alias α-maltosyl α-glucoside), 1.1% of α-maltotriosyl α,α-trehalose(alias α-maltotetraosyl α-glucoside), and 0.4% of other α-glycosylα,α-trehalose, on a dry solid basis, as saccharide-derivatives ofα,α-trehalose. The syrup enhances the effects of substances having anyone of blood flow-promoting effect, antiinflammatory effect,antibacterial effect, moisturizing effect, whitening effect,UV-absorbing effect, UV-scattering effect, antioxidant effect, hairgrowing effect, hair nourishing effect, astringent effect,wrinkle-reducing effect, cell-activating effect and transdermalabsorption-promoting effect. It also has a satisfactory moisturizingeffect without sticky feeling. Therefore, it can be advantageously usedas a material for external dermatological formulation.

EXAMPLE 2

The syrup prepared in Example 1 was spray-dried in a usual manner toprepare an amorphous powder. The product shows a low hygroscopicity anda satisfactory solubility in water, and is advantageously used as amaterial for external dermatological formulation as well as Example 1.

EXAMPLE 3

A saccharified solution, desalted with ion exchangers in H-form andOH-form, prepared in Example 1, was subjected to a column chromatographyusing “DOWEX 50W-X4 (Mg²⁺-form)”, a strong acid cation-exchange resincommercialized by Dow Chemical Company, Michigan, USA. The resin waspacked into four jacketed stainless steel columns having an innerdiameter of 5.4 cm, which were then cascaded in series to give a totalgel bed depth of 20 m. Under the conditions of keeping the inner columntemperature at 55° C., the saccharide solution was fed to the columns ina volume of 5% (v/v) and fractionated by feeding to the columns hotwater heated to 55° C. at an SV (space velocity) of 0.13 to remove highcontent fractions of glucose and maltose, and then high contentfractions of saccharide-derivative of α,α-trehalose were collected. Theresulting saccharide solution was further purified and concentrated, andthen spray-dried to prepare an amorphous powder comprisingsaccharide-derivatives of α,α-trehalose in a high content. The productcontained 70.2% of α-maltosyl α,α-trehalose, 6.1% of α-glucosylα,α-trehalose, 2.1% of α-maltotriosyl α,α-trehalose, and 4.1% of otherα-glycosyl α,α-trehalose, on a dry solid basis, assaccharide-derivatives of α,α-trehalose. Since the product shows a lowhygroscopicity and a satisfactory solubility in water, it isadvantageously used as a material for external dermatologicalformulation as well as Example 1.

EXAMPLE 4

One part by weight of a potato starch dissolved in six parts by weightof water was admixed with “NEOSPITASE”, an α-amylase commercialized byNagase & Co., Ltd., Osaka, Japan, to give a final concentration of0.01%/starch, and adjusted to pH 6.0. The resulting starch suspensionwas kept at 85 to 90° C. to be gelatinized and liquefied simultaneouslyuntil DE 1.0 and heated immediately at 120° C. for five minutes. Then,the solution was rapidly cooled to 55° C., adjusted to pH 7.0, admixedwith 150 units/g-starch on a dry solid basis of “PULULLANASE”, anpullulanase (EC 3.2.1.41) commercialized by Hayashibara BiochemicalLaboratories Inc., Okayama, Japan, and eight units/g-starch on a drysolid basis of maltotetraose-forming amylase, disclosed in JapanesePatent Publication (Kokai) No. 240,784/88, commercialized by HayashibaraBiochemical Laboratories Inc., Okayama, Japan, and followed by theenzymatic reaction at 50° C. and pH 7.0 for 36 hours. After autoclavedat 120° C. for 10 minutes, the reaction mixture was cooled to 53° C.,admixed with 2 units/g-starch of non-reducing saccharide-forming enzymeoriginated from Arthrobacter sp. S34 (FREM BP-6450), disclosed inJapanese Patent Publication (Kokai) No. 228,980/00, and followed theenzymatic reaction for 64 hours. The reaction mixture was kept at 95° C.for 10 minutes, cooled and filtered to obtain a filtrate. According tothe conventional manner, the resulting filtrate was decolored withactivated charcoal, desalted and purified with ion exchangers in H- andOH-forms, and then concentrated. The concentrate was spray-dried toobtain an amorphous powder containing saccharide-derivatives ofα,α-trehalose in a yield of about 90% to the material starch on a drysolid basis. The product showed DE 11.4 and contained 62.5% ofα-maltosyl α,α-trehalose, 2.1% of α-glucosyl α,α-trehalose, 0.8% ofα-maltotriosyl α,α-trehalose, and 0.5% of other α-glycosylα,α-trehalose, on a dry solid basis. Since the product shows a lowhygroscopicity and a satisfactory solubility in water, it is useful as amaterial for external dermatological formulation as well as Example 1.

EXAMPLE 5

Aqueous solution containing 20% of a reagent grade maltotetraose (purity97.0% or higher), commercialized by Hayashibara Biochemical LaboratoriesInc., Okayama, Japan, was admixed with two units/g-saccharide ofnon-reducing saccharide-forming enzyme, disclosed in Japanese PatentPublication (Kokai) No. 143,876/95, and followed by the enzymaticreaction at 46° C. for 48 hours to obtain a saccharide solutioncontaining 79.8% of α-maltosyl α,α-trehalose on a dry solid basis. Afteradjusted to pH 6.0, the saccharide solution was admixed with 10units/g-saccharide of β-amylase, commercialized by Nagase & Co., Ltd.,Osaka, Japan, and followed by the enzymatic reaction at 50° C. for 48hours for the purpose of hydrolyzing maltotetraose. After autoclaved at120° C. for 10 minutes, the reaction mixture was cooled and filtrated.The resulting filtrate was subjected to a column chromatography using“XT-1016 (Na+-form, degree of cross linking 4%)”, a strong acidcation-exchanger resin commercialized by Rohm and Hass Japan K.K.,Fukushima, Japan, to collect fractions highly containing α-maltosylα,α-trehalose. The saccharide solution was purified, concentrated, andspray-dried to obtain an amorphous powder highly containing α-maltosylα,α-trehalose. The product, containing 98.1% of α-maltosylα,α-trehalose, has a low reducing power less than the detection limit ofSomogyi-Nelson method. Since the product shows a low hygroscopicity anda satisfactory solubility in water, it is useful as a material forexternal dermatological formulation. Since the product shows noreducibility, it is advantageously used as a material for externaldermatological formulation comprising compounds inactivated by Maillardreaction such as amino acid and compounds having amino groups.

EXAMPLE 6

The syrup containing saccharide derivatives of α,α-trehalose, preparedin Example 1, was dissolved in water to give a saccharide concentrationof about 60% and admixed with about 8.5% of Raney nickel. The mixturewas autoclaved at 128° C. with stirring and treated with hydrogen at apressure of 80 kg/cm² to convert reducing sugars coexisting withsaccharide-derivatives of α,α-trehalose, such as glucose and maltose,into corresponding sugar alcohols. After separated from Raney nickel,the resulting solution was decolored, desalted, and concentrated toobtain syrup at the concentration of 75%. The product is a non-color andtransparent solution contains about 2.0% of α-glucosyl α,α-trehalose,about 54.3% of α-maltosyl α,α-trehalose, about 1.6% of α-maltotriosylα,α-trehalose, about 5.2% of other saccharide derivatives ofα,α-trehalose, about 4.4% of sorbitol, about 5.4% of maltitol, about9.4% of maltotriitol, about 16.3% of maltotetraitol, and about 1.4% ofother sugar alcohols. The product enhances the effects of substanceshaving any one of blood flow-promoting effect, antiinflammatory effect,antibacterial effect, moisturizing effect, whitening effect,UV-absorbing effect, UV-scattering effect, antioxidant effect, hairgrowing effect, hair nourishing effect, astringent effect,wrinkle-reducing effect, cell-activating effect and transdermalabsorption-promoting effect. The product is stable against the change oftemperature or humidity. It keeps its low hygroscopicity even in a highhumidity condition. Since the product gives skins a smooth feeling andrefresh feeling without sticky feeling and has a satisfactory moistureretaining activity when applied, is suitable as materials for externaldermatological formulations. Since the product has no reducibility, itis particularly suitable as a material for external dermatologicalformulations containing ingredient affect with browning or denaturationdue to Mailard reaction such as amino acids and compounds having aminogroups as well as in Example 1.

Viscosity at 20° C., 30° C., 40° C., 50° C., or 60° C. of this syrup ordiluted solutions thereof (at a concentration of 10%, 20%, 30%, 40%,50%, 60% and 70%, on a dry solid basis), prepared by diluting the syrupin an appropriate amount of purified water, was measured by “B typeViscometer” commercialized by Tokyo Keiki Co. Ltd., Tokyo, Japan. Table5 shows the result. The 10% solution was heated at 120° C. for 30, 60 or90 minutes. The heated samples and the unheated sample (the solutionbefore heating) were measured with absorbance 480 nm to determine thedegree of coloring. And, the content of α-maltosyl α,α-trehalose of eachsample was measured. Table 6 shows the result. The content of α-maltosylα,α-trehalose of each sample was represented by relative value to thatof the unheated sample defined as 100%. TABLE 5 Concentration Viscosity(mPa · s) (Dry solid basis, %) 20° C. 30° C. 40° C. 50° C. 60° C. 10 1 11 1 1 20 3 2 2 1 1 30 4 3 3 2 2 40 9 6 5 4 3 50 26 17 11 8 7 60 139 7746 31 22 70 1772 755 369 200 121 75 8844 3345 1418 666 351

TABLE 6 Content of Heating time Degree of α-maltosyl (minute) coloringα,α-trehalose Unheated 0.009 100 30 0.007 100 60 0.008 100 90 0.011 100

As evidence from the result in Table 6, saccharide derivatives ofα,α-trehalose and co-existing hydrogenated saccharides from reducingsaccharides such as glucose and maltose were not colorized by heating at120° C. for 90 minutes. In addition, α-maltosyl α,α-trehalose ass mainingredient was hardly decomposed. Therefore, the syrup was revealed tobe satisfactorily heat-stable.

Property on Absorbing and Releasing Moisture

Property on absorbing and releasing moisture of the syrup containingsaccharide derivatives of α,α-trehalose (concentration of 75%, on a drysolid basis), prepared in Example 6, was examined by the followingexperiment; saturated solution of magnesium chloride hexahydrous,potassium carbonate dihydrous, magnesium nitrate hexahydrous, ammoniumnitrate, sodium chloride, potassium chloride, barium chloride dihydrous,or potassium sulfate (reagent grade) was prepared by dissolving inpurified water and placed in sealed chamber overnight to give a relativehumidity (RH) of 33.0%, 42.7%, 52.8%, 60.0%, 75.2%, 87.2%, 90.1%, or97.3%. Container without cap containing about 0.5 g of the product wasmeasured and placed in the chamber without contacting the preset saltsolution, and kept at 25° C. After 0.3, 1, 3, 5, 7, 10, and 14 days, thecontainers with the product were measured to calculate the rate ofchange (%) in a manner of comparing each value with the starting weightas 100%. The result is shown in Table 7. TABLE 7 Relative Time course(day) humidity Starting 0.3 1 3 5 7 10 14 33.0 0.0 −5.3 −7.9 −11.1 −12.8−13.5 −14.2 −14.8 42.7 0.0 −5.3 −7.9 −11.0 −12.9 −13.5 −14.2 −14.7 52.80.0 −5.8 −8.4 −11.4 −13.2 −13.8 −14.4 −14.9 60.0 0.0 −5.2 −7.7 −10.7−12.4 −12.9 −13.3 −13.6 75.2 0.0 −2.8 −5.3 −7.7 −9.0 −9.3 −9.2 −9.4 84.20.0 −1.0 −0.5 −0.1 −0.8 −1.0 −0.6 −0.0 90.1 0.0 1.1 3.4 7.2 7.3 9.3 13.411.4 97.3 0.0 4.3 9.8 22.7 26.6 32.4 41.0 47.0

As evidence from result in Table 7, the product exerted the effect onabsorbing moisture in the circumstance of RH 97.3% or 90.1%. The weightof the product increased up about 47.0% or 11.4% to the starting weightafter 14 days. In the circumstance of RH 84.2%, the weight of theproduct did not increased. The results reveal that the product is asyrup hardly absorbing moisture in the condition of relatively highhumidity. The product released moisture in the circumstance of RH 75.2%or lower. Although the weight of the product gradually decreased until 3days, the product stably kept its moisture because the decrease ofweight was not observed after 3 days. The decreasing rate depends onhumidity of circumstance. The lower humidity of circumstance causes themore decreasing rate. Concretely, the weight of the product preserved inthe circumstance of RH 33% for 14 days decreased about 14.8% to startingweight. In contrast, the syrup containing saccharide derivatives ofα,α-trehalose, prepared in Example 1, was decreased in its weight due toreleasing moisture in the circumstance of RH 84.2% that the productshowed no change of weight (data not shown). The syrup prepared Example1 was more decreased in its weight than the product in the circumstanceof RH 75.2% or less. Therefore, hydrogenated syrup, containingsaccharide derivatives of α,α-trehalose and sugar alcohols convertedfrom reducing saccharides, is revealed to have better moisturizingeffect than the non-hydrogenated syrup.

Test for Absorbing or Releasing Moisture

The syrup containing saccharide derivatives of α,α-trehalose wasconfirmed to have a satisfactory property of absorbing and releasingmoisture. To compare other saccharide used as a usual moisturizing agentfor cosmetics, the following experiment was carried out. Test samples,containing 75%, on a dry solid basis, of either of the syrup prepared inExample 6, concentrated glycerin, sorbitol or maltitol, were prepared.About 1 g of each solution was placed in two containers. The containerswere preciously weighed and kept at RH 60% for 216 hours. One ofcontainers was kept at RH 80% and the other container was kept at PH33%. After 24 hours or 168 hours, they were weighed. The relative weightchange rate of each test sample was calculated in such a manner ofcomparing each value with the weight of a control kept at RH 60% for 216hours, which was regarded as 100%. The result is shown in Table 8. TABLE8 Relative weight change rate (%) Time course at RH 80% or 33% (hour)Humidity Test sample 0 24 168 RH 80% Glycerin 0.0 8.2 13.1 Sorbitol 0.05.4 10.7 Maltitol 0.0 3.5 5.3 Syrup 0.0 1.6 3.0 containing saccharidederivatives of α,α-trehalose RH 33% Glycerin 0.0 −13.8 −18.8 Sorbitol0.0 −2.4 −5.0 Maltitol 0.0 −1.4 −4.2 Syrup 0.0 −0.6 −2.3 containingsaccharide derivatives of α,α-trehalose

As evidence from result in Table 8, test samples placed in thecircumstance at RH 80% were rapidly increased in weight until 24 hourslater, and gradually increased after that due to absorbing moisture.Glycerin or sorbitol showed 10% or more of the rate of increasing weightat 168 hours. In contrast, the syrup containing saccharide derivativesof α,α-trehalose showed about 3% which was the lowest of the testsamples. Test samples placed in the circumstance at RH 33% were rapidlydecreased in weight until 24 hours later, and gradually increased afterthat due to releasing moisture. Glycerin showed about 19% of the rate ofdecreasing weight at 168 hours. In contrast, the syrup containingsaccharide derivatives of α,α-trehalose showed about 3% which was thelowest of the test samples. As evident form the above experiment andresult in Experiment 4, the syrup containing saccharide derivatives ofα,α-trehalose is revealed to be saccharides more hardly influenced bythe humidity of the circumstance than glycerin, sorbitol or maltitol asusual cosmetic moisturizing agent in the circumstance at RH 80% or 33%.They were not sticky in higher humidity and keep moisturizing effect inlower humidity, and have a satisfactory property for a controlling agentfor absorbing or releasing moisture. Therefore, the property of thesaccharide derivatives of α,α-trehalose, described above, was suggestedto be due to the excellent controlling effect on absorbing and releasingmoisture.

Single Oral Administration Limiting Test

Five males and five females of five-weeks aged Wister rats,commercialized by Japan Charlsrever Co., Ltd., Tokyo, Japan, wereforcedly administered with 2 g/kg body weight of the syrup containingsaccharide derivatives of α,α-trehalose (at a concentration of 75%, on adry solid basis), prepared in Example 6, in order to carry out singleoral administration limiting test. As a control, five males and fivefemales of five-weeks aged rats were forcedly administered with 2 g/kgbody weight of purified water. Both of the groups administered withsaccharide derivatives of α,α-trehalose and the control group wereobserved in megascopic and anatomic manners and revealed to show nodisorder and death. No variation in their body weight was observedbetween the group administered with saccharide derivatives ofα,α-trehalose and the control group. This single oral administrationlimiting test revealed that the limiting dose of the syrup containingsaccharide derivatives of α,α-trehalose was 2 g/kg or more.

Eye Mucosa-Irritation Test

Eight males and eight females of 3 to 4 months-aged New Zealand Whiterabbits, commercialized by Charles River Japan, Inc., Yokohama, Japan,were once administered in their right eyes with 0.2 g of the syrupcontaining saccharide derivatives of α,α-trehalose (at a concentrationof 75%, on a dry solid basis), prepared in Example 6. As controls, theywere not administrated in their left eyes with the syrup. One hourlater, four male and four female rabbits were washed their eyes withphysiological saline (hereinafter, called “Washed group”). The remainingfour male and four female rabbits were not washed their eyes(hereinafter, called “Unwashed group”). The rabbit eyes of the washedand the unwashed groups were observed about the changes of cornea, irisand conjunctiva just after the administration of saccharide derivativesof α,α-trehalose, just after the eye washing, and one, two and threedays after the eye washing. The rabbits of the washed and unwashedgroups were not observed any change of cornea, iris and conjunctiva atany checking time. The result revealed that the syrup containingsaccharide derivatives of α,α-trehalose gave no irritation.

Test for Cell Activation

To examine the influence of the syrup containing saccharide derivativesof α,α-trehalose, prepared in Example 6, on cell proliferation, thefollowing experiment was carried out. The syrup was diluted withpurified water and sterilized with a 0.22-μm filter to prepare a 60%solution. One volume of the resulting solution was diluted with anappropriate amount of purified water, and admixed with 10 volumes of MEMmedium to prepare test media containing 6%, 0.6%, 0.06% or 0.006% on adry solid basis of the saccharide derivatives of α,α-trehalose. Humanfibroblast cells (NB1RBG), suspended with MEM medium supplemented with1% fetal calf serum, were seeded in a 24-well microplate, and culturedin a 5% CO₂ incubator at 37° C. for one day. After removing medium fromthe wells, either of the above test media was added to the wells andchanged once a day. The cells were continuously cultured for four days.As a control, the cells were cultured in the same manner and scheduleexcept for using a control medium prepared by mixing 10 volumes of MEMmedium to one volume of purified water. The cells were cultured in thewells filled with each test medium with different concentration ofsaccharide mixture containing saccharide derivatives of α,α-trehalose,and subjected to usual MTT assay for measuring cell amount. Each cellamount was represented by a relative value to that of the controldefined as 100%. The result is shown in Table 9. TABLE 9 Concentrationof saccharide mixture containing saccharide derivatives of α,α-trehalose(%, Dry solid basis) Cell amount (%) 0 100 0.006 109 0.06 112 0.6 1216.0 114

As evidence from the result in Table 9, all the test media moreincreased the amount of fibroblast cell than the control medium.Particularly, the cell amount with the test medium containing 0.6% ofthe saccharide mixture showed 21% increase as compared with the controlmedium. The saccharide mixture containing saccharide derivatives ofα,α-trehalose was revealed to have a cell-activating effect.

Test for Cell Protection

To examine the influence of the syrup containing saccharide derivativesof α,α-trehalose, prepared in Example 6, on cell protection, thefollowing experiment was carried out. Mouse fibroblast cells (L-929),suspended in Dulbecco's MEM (hereinafter, called as “D-MEM”)supplemented with 10% fetal calf serum, were seeded in 12 of 6-wellmicroplates and cultured in a 5% CO₂ incubator at 37° C. for 2 days. Thecells placed in four plates were further cultured for one day in thetest medium containing D-MEM supplemented with 10% fetal calf serum and1%, on a dry solid basis, of the syrup containing saccharide derivativesof α,α-trehalose (at the concentration of 75%, on a dry solid basis). Ascontrols, control media containing D-MEM supplemented with 10% fetalcalf serum and optionally containing 1% glycerin were prepared. Thecontrol mediums were added in the medium-removed wells of the remainingfour plates, respectively. The cells were cultured for one day, driedfor one hour in such a manner of keeping in opened plate under thesterile condition after the medium was removed from the wells byaspiration. Then, the cells were cultured in D-MEM supplemented with 10%fetal calf serum for three days while changing the medium once a day.The resulting plates were subjected to the measurement of cell amount ofeach well using “Alamar Blue” commercialized by Wako Pure ChemicalIndustries, Ltd., Osaka, Japan, just after the drying, and four hours,one day, two days or three days after the drying. The amounts of thecells were represented by a relative proliferation rate to that of thecells just after the one-hour-drying defined as 100%. The result isshown in Table 10. In detail, the medium was added to each well in anamount of 4 ml. One plate was used for each measurement for the amountof cells treated with the test medium or the two control mediums. Theaverage value of the measured values from six wells was calculated byadding 401 of “Alamar Blue” to one well and incubating four hours andmeasuring the cell amount by a fluorescence plate reader. The result isshown in Table 10. TABLE 10 Rate of cell proliferation (%) Culturing day(after dried) Medium One hour One day Two days Three days D-MEMcontaining 1% 100 169 262 283 of saccharide mixture containingsaccharide derivatives of α,α-trehalose (Dry solid basis) D-MEMcontaining 1% 100 165 235 243 glycerol D-MEM 100 163 234 238

As evidence from the result in Table 10, the test medium or the controlmedia increased the rate of cell proliferation of fibroblast cells. Thecontrol medium containing 1% of glycerin increased cell amount almostequal to the control medium containing only D-MEM. In contrast, the testmedium showed a higher increase rate of fibroblast cell proliferationthan those with the control media. Influence caused by UV-irradiationwas examined in the same manner as above instead of exposure to a dryingcondition (data not shown). Medium containing 1%, on a dry solid basis,of the saccharide mixture containing saccharide derivatives ofα,α-trehalose showed a higher cell proliferation than the control media(D-MEM or D-MEM containing 1% of glycerin). This result reveals that asaccharide mixture containing saccharide derivatives of α,α-trehalosehas a cell-protecting effect against external stresses such as drying orUV-irradiation.

Test for Prevention of the Rough Skin

To examine the influence of saccharide derivatives of α,α-trehalose onthe rough skin, the following experiment was carried out. A test aqueoussolution containing 10% sodium dodecyl sulfate (hereinafter, abbreviatedas “SDS”) and 20% of the syrup containing saccharide derivatives ofα,α-trehalose was prepared. It was applied to the skin surface at thebody side of the upper arm of subjects according to usual closed patchmethod using “Finnchamber” commercialized by Taisho Pharmaceutical Co.,Ltd., Tokyo, Japan, for two hours. The treated skin surface was observedby magnifying 50 times using “Digital HD microscope VH-7000”commercialized by Keyence Corporation, Osaka, Japan. As a control,purified water was used.

When applied with an SDS solution, the skin surface was suffered fromredness and inflammation. In addition, the skin folds and skin ridgesbecame obscure and the skin texture pattern disappeared. In contrast,when applied with an SDS solution containing saccharide derivatives ofα,α-trehalose, the skin surface was not suffered from inflammation. Inaddition, the skin folds and skin ridges were clear and the skin texturepattern finely and clearly appeared. The result reveals that asaccharide mixture containing saccharide derivatives of α,α-trehaloseeffectively prevents the rough skin due to surfactants such asdetergents.

Test for Acidic Fermentation

To examine the effect of the syrup containing saccharide derivatives ofα,α-trehalose, prepared in Example 6, on acidic fermentation, thefollowing experiment was carried out. The syrup containing saccharidederivatives of α,α-trehalose prepared in Example 6, α-maltosylα,α-trehalose used in Experiment 1, or sucrose was dissolved inStephan's buffer to give a final concentration of 0.7%, on a dry solidbasis, in order to prepare test saccharide solutions. Streptocpccusmutans OMZ-176 or Streptococcus sobrinus 6715, belonging to a kindcariogenetic bacteria, was cultured by the steps of slant culture, seedculture and main culture, and centrifuged to collect a bacteriaprecipitate. The resulting precipitate was washed with Stephan buffer(pH7.0), and centrifuged to collect a bacteria precipitate. Equal volumeof Stephan buffer was added to the bacteria precipitate, followed bysuspending the precipitate in the buffer to give a final concentrationof 50% (v/v) in order to prepare two bacteria suspensions for testing. Ahalf milliliter of the bacteria suspension was admixed with 0.5 ml ofthe above test saccharide solution and incubated at 37° C. for 90minutes, while measuring the pH at 5, 15, 30, 60, and 90 minutes afterthe initiation of the culture. The result is shown in Table 11. TheStephan's buffer was prepared by admixing 1 ml of “solution A” and“solution B” with distilled water to give a final volume 100 ml, andadjusting to pH7.0 (“solution A”: dissolving 71 g of Na₂HPO₄, 7.92 g ofKOH and 68.1 g of KH₂PO₄ in distilled water to give a final volume 1,000ml; and “solution B”: dissolving 45.4 g of KH₂PO₄, 3.2 g of MgSO₄ 2H₂Oand 100 ml of 1.2N HCl in distilled water to give a final volume 1,000ml). TABLE 11 pH Bacterial Test saccharide Reaction time (minute) strainsolution 0 5 15 30 60 90 S.* Syrup containing 6.68 6.61 6.51 6.49 6.426.41 mutans saccharide OMZ-176 derivatives of strain α,α-trehalose,prepared in Example 6 α-Maltosyl 6.72 6.70 6.64 6.58 6.51 6.43α,α-trehalose used in Experiment 1 Sucrose 6.60 4.05 3.97 3.99 3.99 4.01S.* Syrup containing 6.72 6.70 6.64 6.58 6.51 6.43 sobrinus saccharide6715 derivatives of strain α,α-trehalose, prepared in Example 6α-Maltosyl 6.72 6.70 6.64 6.58 6.51 6.43 α,α-trehalose used inExperiment 1 Sucrose 6.74 4.18 3.87 3.81 3.82 3.91Note;S*: Streptococcus

As evidence from the result in Table 11, sucrose decreased pH of thebacterial solution containing Streptcoccus mutans OMZ-176 orStreptococcus sobrinus 67115 from about 6.7 to about 4.0 for fiveminutes. In contrast, the syrup containing saccharide derivatives ofα,α-trehalose, prepared in Example 6, and saccharide derivatives ofα,α-trehalose hardly decreased pH of the bacterial solution even 90minutes later. Therefore, these saccharides were revealed to hardly givethe acidic fermentation with Streptcoccus mutans OMZ-176 orStreptococcus sobrinus 6715.

Test for the Production of Water-Insoluble Glucan

To examine the effect of the syrup containing saccharide derivatives ofα,α-trehalose, prepared in Example 6, on the production ofwater-insoluble glucan, the following experiment was carried out.According to usual method, Streptococcus mutans OMZ-176 was cultured toprepare a crude water-insoluble glucan producing enzyme solution (25 mgprotein/ml). Test saccharide solutions were prepared by dissolving thesyrup prepared in Example 1, the syrup prepared in Example 6, orα-maltosyl α,α-trehalose used in Experiment 1 in purified water to givea final concentration 2% on a dry solid basis. A half milliliter of oneof the test saccharide solution was admixed with 0.25 ml of the crudewater-insoluble glucan producing enzyme solution, 0.75 ml of 0.1 Mphosphate buffer, and 0.5 ml of 2% sucrose. The resulting reactionmixture was placed in a new test tube (sized with 10 mm in diameter and130 mm in height) slanted at an elevation angle of 30 degrees, and keptat 37° C. for 16 hours. The supernatant was gently collected. Theremaining precipitate was washed with deionized water by centrifugingtwice to collect a precipitate as adherent glucan. The washing solutionand the above supernatant was mixed together and centrifuged at 5,000rpm for 10 minutes to collect precipitate. The resulting precipitate waswashed with deionized water and centrifuged to collect a non-adherentglucan. The adherent and non-adherent glucan were weighed. The totalweight thereof was calculated as water-insoluble glucan. As a control,distilled water was used instead of the test saccharide solution. Thewater-insoluble glucan as control were weighed in the same manner.Inhibitory rate (%) of the production of water-insoluble glucan wascalculated in such a manner of dividing the value of each testsaccharide solution by that of the control, multiplying the resultingvalue by 100, and subtracting the resulting value from 100. The resultis shown in Table 12. TABLE 12 Production of water-insoluble glucan(μg/10 mg sucrose) (Inhibition rate of production (%)) AdhesiveNon-adhesive Total Test saccharide solution glucan glucan glucanDistilled water 2222  1166 3388 Syrup containing saccharide 575 10041579 derivatives of α,α-trehalose,  (74)  (14)  (53) prepared in Example1 Syrup containing saccharide 933 1125 2058 derivatives ofα,α-trehalose,  (58)   (4)  (39) prepared in Example 6 α-Maltosylα,α-trehalose, 1120  1009 2129 prepared in Example 1  (50)  (13)  (37)

As evidence form the result in Table 12, all the test saccharidesolutions inhibited the production of water-insoluble glucan fromsucrose.

An additional experiment was carried out in the same manner except forwithout sucrose. As a result, the water-insoluble glucan was notproduced from all test saccharides. These results reveal that saccharidederivatives of α,α-trehalose or saccharide mixtures containing the sameare suitably used in raw materials for oral cosmetics includingtoothpaste to prevent dental caries.

Effect on Antiinflammation

Keratinocyte is known to produce cytokines inducing inflammation(inflammatory cytokines) such as interluekin-1β (hereinafter, it iscalled as “IL-1β”) and TNF-α caused by external stresses illustratedwith the infection of microorganisms, UV or surfactants. Theseinflammatory cytokines act on keratinocytes and enhance the productionof inflammatory cytokine from keratinocytes. In addition, since theyinduce the expression of cell adhesion molecules on keratinocytes orblood vessel endothelial cells at the inflammatory skins, they makewhite blood cells stay there. Therefore, they cause to aggravate theinflammation at inflammatory skins.

To examine the effect of the syrup containing saccharide derivatives ofα,α-trehalose, prepared in Example 6, on the inflammation, the followingexperiment that the production of TNF-α and expression of ICAM-1, one ofthe cell adhesion molecules were examined using HaCat cell, a kind ofkeratinocyte cell line, was carried out. Keratinocyte cell line HaCatcells were suspended in RPMI-1640 medium supplemented with 10% fetalcalf serum, seeded by 5×10⁴ cells/well in 96-well microplate andcultured overnight. After removed from the medium, the cells was admixedwith RPMI-1640 supplemented with 10% fetal calf serum containing 2%, 1%,0.5% or 0.2% (w/v) of the syrup prepared in Example 6 or concentratedglycerin (cosmetic grade) and 1 ng/ml of IL-1β, and incubated for sixhours. The resulting supernatants were subjected to enzyme immunoassayusing HRPO-labeled anti-human TNF-α antibody in order to measure theamount of TNF-α. To measure the amount of ICAM-1 expression, theresulting cells were fixed with 3.7% formalin, applied with anti humanICAM-1 antibody, and admixed with 4-methyl-umbelliferylβ-D-galactopyranoside. The resulting microplates were provided tofluorescent plate reader (excitation wavelength 355 nm, measurementwavelength 460 nm) in order to measure fluorescent intensity. As acontrol, cells were cultured in the only medium with the same stimulantto provide to the measurement of amount of TNF-α or ICAM-1 molecule.Inhibitory rate (%) of the production of TNF-α or ICAM-1 was calculatedin a manner of dividing the value of each test medium by that of controlmedium and subtracting 100 times the resulting value from 100. Theresult of the inhibitory rate of the production of TNF-α is shown inTable 13, and that of ICAM-1 is shown in Table 14. TABLE 13 Inhibitoryrate of the production of TNF-α Concentration of syrup containingsaccharide derivatives of α,α-trehalose or glycerin (%) Kind of medium2.0 1.0 0.5 0.25 RPMI-1640 medium containing 59 72 87 92 saccharidederivatives of α,α-trehalose RPMI-1640 medium containing 146 146 133 123glycerin

TABLE 14 Inhibitory rate of the production of ICAM-1 Concentration ofsyrup containing saccharide derivatives of α,α-trehalose or glycerin (%)Kind of medium 2.0 1.0 0.5 0.25 RPMI-1640 medium containing 62 71 82 84saccharide derivatives of α,α-trehalose RPMI-1640 medium containing 8989 90 91 glycerin

As evident from the result shown in Table 13 or 14, the syrup containingsaccharide derivatives of α,α-trehalose inhibited the production ofTNF-α and ICAM-1 molecule of the keratinocyte cell line HaCat cellstimulated with IL-1β in a concentration-dependent manner. Glycerinenhanced the production of TNF-α in a concentration-dependent manner andinhibited the production of ICAM-1 molecule. However, glycerin showedlower inhibitory rate than the syrup containing saccharide derivativesof α,α-trehalose did. Result of MTT method, carried out by each wellafter the experiment, showed almost no lowering of viability of thecell. According to the same experiment except for using macrophage cellline RAW264.7 and IFN-γ and LPS as stimulants, the syrup containingsaccharide derivatives of α,α-trehalose or glycerin inhibited theproduction of TNF-α in a concentration-dependent manner. However, thesyrup showed higher inhibitory rate than glycerin did at anyconcentration (data not shown).

These results suggest that saccharide derivatives of α,α-trehalose arecapable of inhibiting the inflammation by applying to skin surfacelowered in barrier function by the destruction of horny layers due torough skin or inflammation, or to inflammatory head skins or mucosae.Therefore, the syrup containing saccharide derivatives of α,α-trehaloserevealed to be safe and suitable as raw materials havingantiinflammatory effect for external dermatological formulations.

Test for Antielectrostatic Property

To examine the effect of the syrup containing saccharide derivatives ofα,α-trehalose, prepared in Example 6, on the antielectrostatic property,the following experiment was carried out. The syrup prepared in Example6 was dropped on an acrylic plastic board and uniformly applied using abar coater to prepare acrylic plastic board coated with a film 25 μmdepth. Then, the conductance was measured by attaching the electro-rodon the surface of the acrylic plastic board. The conductor of the coatedsurface was 3×10¹¹ ohm. While, that of the uncoated surface was 1×10¹⁵ohm. The half life of static electricity was measured by neostmeter. Thecoated surface was 20 seconds or less. While, that of the uncoatedsurface was one minute or more. The acrylic plastic board coated withthe syrup was lower than usual antielectrostatic acrylic plastic boardsin the surface resistance and the half life of static electricity. Thatmeans electric charges generated by electrostatic phenomenon are quicklyeliminated. The result reveals that the saccharide mixture containingsaccharide derivatives of α,α-trehalose lower the static electricity onthe applied surface. Therefore, the syrup is suggested to be capable ofinhibiting the damages due to electrostatic phenomenon.

EXAMPLE 7

The amorphous powder, containing saccharide derivatives ofα,α-trehalose, prepared in Example 3, was dissolved in water to give asaccharide concentration of about 60% was admixed with about 9% of Raneynickel. The mixture was autoclaved at 130° C. with stirring and treatedwith hydrogen at a pressure of 75 kg/cm² to convert reducing sugarscoexisting with saccharide-derivatives of α,α-trehalose, such as glucoseand maltose, into corresponding sugar alcohols. After separated fromRaney nickel, the resulting solution was decolored, desalted, andconcentrated to obtain syrup at a concentration of 75%. Further, thesyrup was spray-dried in a usual manner to obtain an amorphous powder.The product, containing about 70% of α-maltosyl α,α-trehalose and about12% of other saccharide derivatives of α,α-trehalose on a dry solidbasis, shows a low hygroscopicity and a satisfactory water-solubilityand advantageously used as materials for external dermatologicalformulation as well as Example 1.

EXAMPLE 8

About 6% starch suspension of potato starch was gelatinized by heating,adjusted to pH4.5 at 50° C., admixed with 2,500 units/g-starch ofisoamylase commercialized by Hayashibara Biochemical Laboratories, Inc.,Okayama, Japan and followed by the enzyme reaction for 20 hours. Theresulting reaction mixture was adjusted to pH6.0 and autoclaved at 120°C. for 10 min. After cooled to 45° C., the reaction mixture was admixedwith 150 units/g-starch of “TERMAMYL 60L”, an α-amylase commercializedby NovoZyme A/S, Bagsværd, Denmark and followed by the enzyme reactionfor 24 hours. The reaction mixture was autoclaved at 120° C. for 20minutes. After cooled to 45° C., the reaction mixture was admixed with 2units/g-starch of non-reducing saccharide-forming enzyme originated fromArthrobacter sp. Q36 (FREM BP-4316), disclosed in Japanese PatentPublication (Kokai) No. 143,876/95, and followed by the enzymaticreaction for 64 hours. The reaction mixture was kept at 95° C. for 10minute, cooled and filtered to obtain a filtrate. According to theconventional manner, the resulting filtrate was decolored with activatedcharcoal, desalted and purified with ion exchangers in H- and OH-forms,and then concentrated into a 65% syrup in a yield of about 89% to thematerial starch on a dry solid basis. The product contains 3.2% ofα-glucosyl α,α-trehalose, 6.5% of α-maltosyl α,α-trehalose, 28.5% ofα-maltotriosyl α,α-trehalose, and 11.9% of α-glycosyl α,α-trehalosehaving six glucose residues or more. The product is used as materialsfor external dermatological formulation as well as Example 1.

The product was hydrogenated according to the method in Example 7 toconvert coexisting reducing saccharides such as glucose and maltose intocorresponding sugar alcohol. The product, containing about 50% ofsaccharide derivatives of α,α-trehalose (about 6% of α-maltosylα,α-trehalose) on a dry solid basis, is advantageously used as materialsfor external dermatological formulation as well as Example 1. Since theproduct shows no reducibility, it is particularly suitable as materialsfor external dermatological formulations comprising ingredientsinactivated by Maillard reaction.

EXAMPLE 9

Thirty three percent of starch suspension was admixed with calciumcarbonate to give a final concentration of 0.1%, and adjusted to pH 6.0.The resulting solution was admixed with 0.2%/g-starch on a dry solidbasis of “TERMAMYL 60L”, an α-amylase commercialized by NovoZyme A/S,Bagsværd, Denmark, and followed by the enzymatic reaction at 95° C. for15 minutes. After autoclaved at 120° C. for 30 minutes, the reactionmixture was cooled to 50° C., admixed with 500 units/g-starch ofisoamylase, commercialized by Hayashibara Biochemical Laboratories Inc.,Okayama, Japan and 1.8 units/g-starch of maltohexaose maltoheptaoseproducing amylase, and followed by the enzymatic reaction for 40 hours.The reaction mixture was autoclaved at 120° C. for 10 minutes, cooled to53° C., adjusted to pH 5.7, and admixed with 2 units/g-starch ofnon-reducing saccharide-forming enzyme originated from Arthrobacter sp.S34 (FREM BP-6450), disclosed in Japanese Patent Publication (Kokai) No.228,980/00, and followed the enzymatic reaction for 64 hours. Thereaction mixture was kept at 95° C. for 10 minutes, cooled and filteredto obtain a filtrate. According to the conventional manner, theresulting filtrate was decolored with activated charcoal, desalted andpurified with ion exchangers in H- and OH-forms, and concentrated toprepare a syrup containing saccharide derivatives of α,α-trehalose.Further, the syrup was spray-dried to obtain an amorphous powder as amoisture variation inhibiting agent in a yield of about 87% to thematerial starch on a dry solid basis. The product contains 8.2% ofα-glucosyl α,α-trehalose, 6.5% of α-maltosyl α,α-trehalose, 5.6% ofα-maltotriosyl α,α-trehalose, and 21.9% of α-maltotetraosylα,α-trehalose, 9.3% of α-maltopentaosyl α,α-trehalose, and 14.1% ofα-glycosyl α,α-trehalose having eight glucose residues or more. Sincethe product shows a low hygroscopicity and a satisfactory solubility inwater, it is advantageously used as materials for externaldermatological formulation, if necessary, it is further purifiedaccording to a usual manner for the purpose of increasing the content ofsaccharide derivatives of α,α-trehalose.

The product was hydrogenated according to the method in Example 7 toconvert coexisting reducing saccharides such as glucose and maltose intocorresponding sugar alcohol, purified, and concentrated to obtain asyrup containing saccharide derivatives of α,α-trehalose and sugaralcohols such as sorbitol and maltitol. Further, the syrup wasspray-dried to prepare an amorphous powder in a usual manner. Theproduct, containing about 6% of α-maltosyl α,α-trehalose and about 59%of other saccharide derivatives of α,α-trehalose on a dry solid basis,has a low hygroscopicity and satisfactory water-solubility, even iffurther purified to increase the content of saccharide derivatives ofα,α-trehalose, and advantageously used as materials for externaldermatological formulations as well as Example 1. Since the productshows no reducibility, it is particularly suitable for externaldermatological formulations comprising ingredients inactivated byMaillard reaction.

EXAMPLE 10

Seventy parts by weight of the powder, containing saccharide derivativesof α,α-trehalose, prepared in Example 2, was admixed with 30 parts byweight of “MABIT®”, an anhydrous crystalline maltitol commercialized byHayashibara Shoji Inc., Okayama, Japan, to obtain a powdery mixture. Theproduct is advantageously used as materials for external dermatologicalformulations.

EXAMPLE 11

Seventy parts by weight of the powder, containing saccharide derivativesof α,α-trehalose, prepared in Example 7, was admixed with two parts byweight of “AA2G®”, an L-ascorbic acid 2-glucoside commercialized byHayashibara Biochemical Laboratories, Inc., Okayama, Japan and two partsby weight of “αG RUTIN”, a glycosyl rutin commercialized by HayashibaraBiochemical Laboratories, Inc., Okayama, Japan, to obtain a powderymixture. The saccharide derivatives of α,α-trehalose contained in theproduct enhance the effect of the substances having blood flow-promotingeffect and/or antiinflammatory effect. In addition, since the saccharidederivatives of α,α-trehalose and/or glycosyl rutin inhibit theoxidation, decomposition and denaturation of co-existing ingredientssuch as base ingredients for external dermatological formulations,substances having emulsifying effect, perfumeries, colorants, tanninliquids, honey, beewax, propolis and amino acids, they inhibit theproduction of browning, discoloration and foreign smell. Therefore, theproduct is advantageously used as materials for external dermatologicalformulations.

EXAMPLE 12

Seventy parts by weight of the powder, containing saccharide derivativesof α,α-trehalose, prepared in Example 7, was admixed with two parts byweight of “AA2G®” an L-ascorbic acid 2-glucoside commercialized byHayashibara Biochemical Laboratories, Inc., Okayama, Japan and two partsby weight of “αG HESPERIDIN, a glycosyl hesperidin commercialized byHayashibara Biochemical Laboratories, Inc., Okayama, Japan, to obtain apowdery mixture. The saccharide derivatives of α,α-trehalose containedin the product enhance the effect of the substances having bloodflow-promoting effect and/or antiinflammatory effect. In addition, sincethe saccharide derivatives of α,α-trehalose and/or glycosyl hesperidininhibit the oxidation, decomposition and denaturation of co-existingingredients such as base ingredients for external dermatologicalformulations, substances having emulsifying effect, perfumeries,colorants, tannin liquids, honey, beeswax, propolis and amino acids,they inhibit the browning, discoloration and generation of foreignsmell. Therefore, the product is advantageously used as materials forexternal dermatological formulations.

EXAMPLE 13

Eighty parts by weight of the syrup containing saccharide derivatives ofα,α-trehalose, prepared in Example 6, and 20 parts by weight of hydrouscrystalline trehalose (reagent grade, purity 99.0% or more)commercialized by Hayashibara Biological Laboratories Inc., Okayama,Japan, were mixed together to prepare a syrup. The product isadvantageously used as materials for external dermatologicalformulation.

EXAMPLE 14

Cosmetic Soap

96.5 parts by weight of a neat soup, prepared by saponifying tallow andpalm oil in the rate of 4:1 by weight, and salting out in a usualmanner, was admixed with 1.5 parts by weight of the powder containingsaccharide derivatives of α,α-trehalose, prepared in Example 3, 0.5 partby weight of “AA2G®”, an L-ascorbic acid 2-glucoside commercialized byHayashibara Biochemical Laboratories, Inc., Okayama, Japan, 0.5 part byweight of sucrose, 0.5 part by weight of “αG RUTIN”, a glycosyl rutincommercialized by Hayashibara Biochemical Laboratories, Inc., Okayama,Japan, one part by weight of maltitol, 0.0001 part by weight of Kanko-soNo. 201, and an appropriate amount of perfumeries, and mixed gently. Theresultant was poured into molds, cooled and solidified to obtain a soap.The product is a soap having a whitening effect due to L-ascorbic acid2-glucoside, and has a satisfactory skin feeling without desiccatingafter used. Since the product is inhibited in the oxidation,decomposition and denaturation of base ingredients for soaps, substanceshaving emulsifying effect, perfumeries or colorants by the saccharidederivatives of α,α-trehalose and/or glycosyl rutin, they are inhibitedin the browning, discoloration and the generation of foreign smell in along period. Therefore, the product keeps to have a high quality for along period. In addition, the product is a transparent soap, which isimproved in the problem of conventional soaps containing saccharides,such as cloud and yellowing, because of containing the saccharidederivatives of α,α-trehalose.

EXAMPLE 15

Face Wash

Ten parts by weight of trehalose monomyristate, one part by weight ofglyceryl dioleate, 15 parts by weight of myristinic acid, five parts byweight of liquid paraffin, eight parts by weight of glycerin, four partsby weight of the syrupy saccharide derivatives of α,α-trehalose,prepared in Example 6, 0.2 part by weight of methyl paraoxybenzoate, 0.1part by weight of edetate salts, 0.8 part by weight of glycyrrhizin, 0.4part by weight of potassium hydroxide, 15 parts by weight ofN-methyl-2-prrolidone, and an appropriate amount of citrus flavor weremixed and admixed with water to give a final weight of 100 parts inorder to obtain a face wash. The product, enhanced in theantiinflammatory effect of glycyrrhizin by the saccharide derivatives ofα,α-trehalose, is a face wash having a satisfactory moisturizing effectand skin feeling without sticky feeling after used.

EXAMPLE 16

Bath Salt

Forty four parts by weight of sodium sulfate, 14 parts by weight ofsodium bicarbonate, seven parts by weight of sodium carbonate, 21 partsby weight of succinic acid, five parts by weight of the powdercontaining saccharide derivatives of α,α-trehalose, prepared in Example7, and an appropriate amount of lubricant, colorants and perfumerieswere mixed homogeneously, and tableted to obtain a bath salt. Theproduct produces carbonic acid gas having blood flow-promoting effectwhen entered into bathtub. It is a bath salt having a satisfactory skinfeeling without sticky feeling after used.

EXAMPLE 17

Bath Salt

Forty parts by weight of sodium sulfate, 26 parts by weight of sodiumbicarbonate, 20 parts by weight of sodium carbonate, five parts byweight of “αG HESPERIDIN”, a glycosyl hesperidin commercialized byHayashibara Shoji, Inc., Okayama, Japan, 7.5 parts by weight of thepowder containing saccharide derivatives of α,α-trehalose, prepared inExample 2, 2.5 parts by weight of “Trehalose”, a crystalline hydroustrehalose commercialized by Hayashibara Biochemical Laboratories, Inc.,Okayama, Japan, and an appropriate amount of perfumeries were mixedhomogeneously to obtain a powdery bath salt. The product has asatisfactory blood flow-promoting effect due to the glycosyl hesperidin,and is a bath salt having a satisfactory skin feeling without stickyfeeling after used. When the product was used by seven panels withatopic diseases, it got the answers from all seven panels that itimproved the symptoms of atopic diseases.

EXAMPLE 18

Eye Shadow

6.0 parts by weight of talc, 10.0 parts by weight of “Trehalose”, anα,α-trehalose commercialized by Hayashibara Biochemical Laboratories,Okayama, Japan, five parts by weight of the powder containing saccharidederivatives of α,α-trehalose, prepared in Example 7, 60.0 parts byweight of muscovite, 8.0 parts by weight of ultramarine, 3.0 parts byweight of yellow iron oxide, 1.0 part by weight of black iron oxide and0.1 part by weight of indomethacin were mixed together by a henschelmixer. To the resultant was sprayed seven parts by weight of aheat-dissolved mixture containing 4.0 parts by weight of squalane, 1.9parts by weight of cetyl 2-ethylhexanoate, 0.8 part by weight ofsorbitan sesquioleate, 0.1 part by weight of antiseptics and 0.2 part byweight of colorants and mixed together. The resultant was pulverized andplaced into inner containers to obtain an eye shadow. The product has asatisfactory antiinflammatory effect due to indomethacin and hardlycauses dermatitis even if contacted with skins. The product is capableof freshly making up and satisfactorily keeping the makeup bymoisturizing effect of saccharide derivatives of α,α-trehalose.

EXAMPLE 19

Brusher

12.6 parts by weight of talc, 74.9 parts by weight of sericite, 0.2 partby weight of the powder containing saccharide derivatives ofα,α-trehalose, prepared in Example 7, 0.1 part by weight of ultramarine,0.4 part by weight of yellow iron oxide, 0.4 part by weight of red ironoxide, 0.4 part by weight of Red No. 226, and 0.1 part by weight ofazulene were mixed together by a henschel mixer. To the resultant wassprayed 8.4 parts by weight of a heat-dissolved mixture containing 3.0parts by weight of squalane, 5.0 parts by weight of 2-ethylhexylpalmitate, 0.3 part by weight of antiseptics and 0.1 part by weight ofperfumeries and mixed together. The resultant was pulverized, admixedwith 3.0 parts by weight of titan mica and placed into inner containersto obtain a brusher. The product has a satisfactory antiinflammatoryeffect due to azulene and hardly causes dermatitis even if contactedwith skins. The product is capable of freshly making up andsatisfactorily keeping the makeup by moisturizing effect of saccharidederivatives of α,α-trehalose

EXAMPLE 20

Powder Foundation

2.0 parts by weight of titanium oxide, 10.0 parts by weight of talc, 3.0parts by weight of muscovite, 55.0 parts by weight of sericite, threeparts by weight of the powder containing saccharide derivatives ofα,α-trehalose, prepared in Example 7, 1.0 part by weight of “Trehalose”,an α,α-trehalose commercialized by Hayashibara Biochemical Laboratories,Inc., Okayama, Japan, 12.0 parts by weight of nylon powder, 0.5 part byweight of red iron oxide, 1.0 part by weight of yellow iron oxide, 0.1part by weight of black iron oxide, and 0.1 part by weight of allantoinwere mixed by a henschel mixer. To the resultant was added aheat-resolved mixture containing 1.0 part by weight of silicon oil, 9.0part by weight of ethyl hexyl palmitate, 2.0 parts by weight of thepowder containing saccharide derivatives of α,α-trehalose, prepared inWxample 7, 1.0 part by weight of sorbitan sesquioleate, 0.3 part byweight of antiseptics and 0.1 part by weight of perfumeries and mixed.The resultant was pulverized and placed into inner containers to obtaina powder foundation. The product has a satisfactory antiinflammatoryeffect due to allantoin and hardly causes dermatitis even if contactedwith skins. The product is capable of freshly making up andsatisfactorily keeping the makeup by moisturizing effect of saccharidederivatives of α,α-trehalose and has a satisfactory skin feeling withoutsticky feeling.

EXAMPLE 21

Foundation

3.5 parts by weight of cetanol, four parts by weight of deodorizedlanolin, five parts by weight of jojoba oil, two parts by weight ofvaseline, six parts by weight of squalane, 2.5 parts by weight ofmonoglyceryl stearate, 1.5 parts by weight of polyoxyethylene(60) casterwax, one part by weight of polyoxyethylene(25) cetyl ether, 0.2 part byeight of γ-oryzanol, 0.2 part by weight of perfumeries, three parts byweight of glycerin, eight parts by weight of propylene glycol, 12 partsby weight of a preparated powder, three parts by weight of allantoin,three parts by weight of the syrup containing saccharide derivatives ofα,α-trehalose, prepared in Example 6, an appropriate amount ofion-exchange water to give a final weight of 100 parts in order toobtain a foundation. The product, enhanced in the antiphlogistic effectof γ-oryzanol by the saccharide derivatives of α,α-trehalose, is afoundation having a satisfactory skin feeling without sticky feelingafter used.

EXAMPLE 22

Absorption Ointment

Forty parts by weight of vaseline, 15 parts by weight of stearylalcohol, 15 parts by weight of Japan wax, 15 parts by weight ofpolyethylene(10) oleate, 0.25 part by weight of monoglyceryl stearate,three parts by weight of pantothenyl alcohol, 3.0 parts by weight of thesyrup containing saccharide derivatives of α,α-trehalose, prepared inExample 6, and an appropriate deionized water were mixed together in ausual manner to obtain an absorption ointment. The product, enhanced inthe antiphlogistic effect of pantothenyl alcohol by the saccharidederivatives of α,α-trehalose, is an absorption ointment having asatisfactory skin feeling without sticky feeling after used.

EXAMPLE 23

Hair Tonic

Fifty parts by weight of ethanol, 1.5 parts by weight ofpolyoxyethylene(8) oleate, 0.1 part by weight of hinokithiol, 1.0 partby weight of glycyrrhizin, 0.01 part by weight of Kanko-so No. 301, fiveparts by weight of trehalose, 10 parts by weight of the syrup containingsaccharide derivatives of α,α-trehalose, prepared in Example 6, 0.1 partby weight of ethylparaben, 0.05 part by weight of perfumeries, and anappropriate amount of deionized water were admixed together in a usualmanner to obtain a hair tonic. The product, enhanced in the hair growingand hair nourishing effect of Kanko-so No. 301 and the antiphlogisticeffect of glycyrrhizin by the saccharide derivatives of α,α-trehalose,is a hair tonic having a satisfactory skin feeling without stickyfeeling after used.

EXAMPLE 24

Cosmetic Cream

Two parts by weight of polyoxyethylene glycol monostearate, five partsby weight of glyceryl monostearate self-emulsifying, one part by weightof behenyl alcohol, two parts by weight of eicosatetraenoic acid, fiveparts by weight of liquid paraffin, 10 parts by weight of glyceryltrioctanate, and an appropriate amount of antiseptics were heat-resolvedin a usual manner. The resulting mixture was admixed with two part byweight of the syrup containing saccharide derivatives of α,α-trehalose,prepared according to the method in Example 6, five parts by weight ofsodium dl-lactate, five parts by weight of 1,3-butylene glycol, one partby weight of ginseng extract, and 65 parts by weight of purified water.The resulting mixture was emulsified by a homogenizer and admixed withan appropriate amount of perfumeries with stirring to obtain a cream.The product is enhanced in the blood flow-promoting effect of ginsengextract by the saccharide derivatives of α,α-trehalose, and lowered inthe unpleasant smell of ingredients such as a substance havingemulsifying effect. The product is a whitening cream stably keeping itshigh quality without browning. In addition, since the product is capableof inhibiting the oxidation and decomposition of lipid from sweat, dirt,scurf or sebum, it can be advantageously used for lowering body odor,preventing the stimulation or itch on skins, or treating or preventingchromatophathy. The product is a cream having a satisfactory skinfeeling without sticky feeling when applied on skins.

EXAMPLE 25

Cosmetic Cream

Two parts by weight of polyoxyethylene glycol monostearate, five partsby weight of glyceryl monostearate self-emulsifying, three parts byweight of behenyl alcohol, two parts by weight of eicosatetraenoic acid,five parts by weight of liquid paraffin, 10 parts by weight of glyceryltrioctanate, and an appropriate amount of antiseptics were mixed andheat-dissolved. The resulting mixture was admixed with 1.6 parts byweight of the syrup containing saccharide derivatives of α,α-trehalose,prepared in Example 7, two parts by weight of “AA2G®”, an L-ascorbicacid 2-glucoside commercialized by Hayashibara Biochemical Laboratories,Inc., Okayama, Japan, 0.1 part by weight of sodium hyaluronate, 0.1 partby weight of dipotassium glycyrrhizinate, 0.1 part by weight of aloeextract, 0.05 part by weight of balm mint extract, 0.05 part by weightof chamomile extract, 0.5 part by weight of “αG HESPERIDIN”, a glycosylhesperidin commercialized by Hayashibara Biochemical Laboratories, Inc.,Okayama, Japan, one part by weight of indigo ethanol extract, five partsby weight of sodium dl-lactate, five parts by weight of 1,3-butyleneglycol, and 66 parts by weight of purified water, and emulsified byhomogenizer. The resulting emulsion was admixed with an appropriateamount of perfumeries with stirring to obtain a cream. The product,enhanced in the blood flow-promoting effect of glycyrrhizinic acid,glycosyl hesperidin and/or indigo ethanol extract by the saccharidederivatives of α,α-trehalose, is advantageously used for preventing thestimulation or itch on skins, or treating or preventing chromatophathysuch as liver spot, freckling and sunburn, and aging of skins. Since theproduct has a low stimulation against skins and a satisfactorymoisturizing effect given by the saccharide derivatives of α,α-trehalosecontained therein, it can be used without care of hypersensitivity. Theproduct is a cream having a satisfactory skin feeling without stickyfeeling when applied on skins.

EXAMPLE 26

Cosmetic Cream

Three parts by weight of polyglyceryl(10) stearate, 0.5 part by weightof stearyl alcohol, three parts by weight of behenyl alcohol, one partby weight of butylalcohol, one part by weight of cetyl palmitate, onepart by weight of glyceryl stearate, one part by weight of fatty acid(C10-30, cholesteryl/lanosteryl), four parts by weight of isopropylpalmitate, five parts by weight of squalane, five parts by weight ofoctyldodecyl myristate, 0.5 part by weight of Macadamia nut oil, 1.8parts by weight of trioctanoin, 0.3 part by weight of dimethicone, sixparts by weight of 1,3-butylene glycol, 2.5 parts by weight of pentyleneglycol, 0.1 part by weight of dipotassium glycyrrhizinate, five parts byweight of the syrup containing saccharide derivatives of α,α-trehaloseat a concentration of 75%, on a dry solid basis, prepared in Example 6,five parts by weight of concentrated glycerin, 15.63 parts by weight ofa solution comtaining two parts by weight of ascorbic acid 2-glucoside,2.33 parts by weight of 10% aqueous solution of sodium hydroxide, onepart by weight of 10% aqueous solution of sodium citrate and 10 parts byweight of purified water, and 37.62 parts by weight of purified waterwere admixed together to obtain a cream. The cream was prepared byemulsifying in the manner of heating with stirring at 4,000 rpm for fiveminutes using homomixer and cooling with stirring. The product, enhancedin the antiinflammatory effect of glycyrrhizinic acid by the saccharidederivatives of α,α-trehalose, is advantageously used for preventing thestimulation or itch on skins, or treating or preventing chromatophathysuch as liver spot, freckling and sunburn, and aging of skins. Thesaccharide derivatives of α,α-trehalose contained therein enable toeasily emulsify and improve the working efficiency to produce a creameven if containing ascorbic acid 2-glucoside. In addition, since theproduct has a low stimulation against skins and a satisfactorymoisturizing effect, it can be used without care of hypersensitivity.The product is a cream having a satisfactory skin feeling without stickyfeeling when applied on skins.

A cream was produced by the same method in Example 26 except foradmixing five parts by weight of concentrated glycerin instead of fiveparts by weight of the syrup containing saccharide derivatives ofα,α-trehalose. 0.15 part by weight of this cream or the cream preparedin Example 26 was admixed with 99.85 parts by weight of purified waterwith stirring for five minutes. Each resulting solution was placed in acell for measurement of particle size and subjected to the measurementof emulsifying particle distribution using “SA-CP3L”, a centrifugalsedimentation particle size distribution measuring instrumentcommercialized by Shimazu Corporation, Kyoto, Japan. The result wasshown in Table 15. TABLE 15 Rate of the particle size distribution (%)Cream containing Cream containing base saccharide derivatives Particlesize (μm) ingredient of α,α-trehalose 300-200 8.3 1.4 200-100 27.0 4.5100-50 0 0  50-20 4.4 9.3  20-10 29.3 33.4  10-5 25.2 44.7  5-2 4.6 5.1 2 or less 1.1 1.5 Median of Particle 16.5 9.9 size (μm)

As evidence from the result in Table 15, the particles sized with 2-20μm occupied about 83% of the total particles in the cream containing thesyrup containing saccharide derivatives of α,α-trehalose. The particlessized with 100 μm or more slightly occupied about 15% of the totalparticles. The median of particle size was 9.9 μm. In contrast, theparticles sized 100 μm or more occupied about 35% of the total particlesin the cream containing concentrated glycerin without saccharidederivatives of α,α-trehalose. The median of particle size was 16.5 μm.As a result, saccharide mixture containing saccharide derivatives ofα,α-trehalose was capable of producing a cream having uniform and smallparticles than glycerin. Microscopic observation of the emulsion stateshowed the same result to the measurement of particle size distribution,although photographic evidence was not shown.

EXAMPLE 27

Cosmetic Cream

Two parts by weight of polyoxyethylene glycol monostearate, five partsby weight of glyceryl monostearate self-emulsifying, three parts byweight of behenyl alcohol, two parts by weight of eicosatetraenoic acid,five parts by weight of liquid paraffin, 10 parts by weight of glyceryltrioctanate, and an appropriate amount of antiseptics were mixed andheat-dissolved. The resulting mixture was admixed with 2.6 parts byweight of the syrup containing saccharide derivatives of α,α-trehalose,prepared in Example 6, two parts by weight of “AA2G®”, an L-ascorbicacid 2-glucoside commercialized by Hayashibara Biochemical Laboratories,Inc., Okayama, Japan, 1.5 parts by weight of “αG RUTIN”, a glycosylrutin commercialized by Hayashibara Biochemical Laboratories, Inc.,Okayama, Japan, 0.1 part by weight of sodium hyaluronate, 0.1 part byweight of dipotassium glycyrrhizinate, 0.1 part by weight of aloeextract, 0.05 part by weight of balm mint extract, 0.05 part by weightof chamomile extract, one part by weight of indigo ethanol extract, 0.5part by weight of EDTA 2Na, 4.5 parts by weight of sodium dl-lactate,five parts by weight of 1,3-butylene glycol, and 66 parts by weight ofpurified water, and emulsified by homogenizer. The resulting emulsionwas admixed with an appropriate amount of perfumeries with stirring toobtain a cream. The product, enhanced in the blood flow-promoting effectof glycyrrhizinic acid and/or indigo ethanol extract by the saccharidederivatives of α,α-trehalose, is advantageously used for preventing thestimulation or itch on skins, or treating or preventing chromatophathysuch as liver spot, freckling and sunburn, and aging of skins. Since theproduct has a low stimulation against skins and a satisfactorymoisturizing effect given by the saccharide derivatives ofα,α-trehalose, it can be used without care of hypersensitivity. Theproduct is a cream having a satisfactory skin feeling without stickyfeeling when applied on skins. The saccharide derivatives ofα,α-trehalose, EDTA-2Na as a chelating agent, dl-sodium lactate andglycosyl rutin inhibit the oxidation, decomposition and denaturation ofbase ingredients for soaps, substances having emulsifying effect,perfumeries or colorants, they inhibit the browning, discoloration andgeneration of foreign smell in a long period. Therefore, the productkeeps its quality for a long period.

EXAMPLE 28

Cosmetic Cream

Forty five parts by weight of purified water, four parts by weight ofthe syrup containing saccharide derivatives of α,α-trehalose, preparedin Example 6, 1.5 parts by weight of 1,3-butylene glycol as a stickeningagent, 2.5 parts by weight of “Sepigel 305”, a polymer composed bypolyacrylamide, C13-C14 isoparaffin and raures-7 commercialized byShibahashi Chemifa, Co., Ltd., Tokyo, Japan, were mixed with stirring inan ambient temperature. Fifty three parts by weight of the resultingmixture was gradually admixed with a heat-melted mixture containing 1.5parts by weight of squalane, two parts by weight of isopropyl palmitate,1.5 parts by weight of octyldodecyl myristate, 1.5 parts by weight ofjojoba oil, one part by weight of silicon and 0.15 part by weight ofmethylparaben in a manner of heating to 80° C. and cooling to 55° C. inorder to prepare an oily phase mixture. 60.65 parts by weight of theoily phase mixture was gradually admixed with aqueous phase mixtureprepared by mixing 0.05 part by weight of glycyrrhizinic acid dissolvedin 29.8 parts by weight of purified water, one part by weight of1,3-butylene glycol, 2.5 parts by weight of 1,2-pentandiol and six partsby weight of concentrated glycerin together, and stirred in a usualmanner to obtain a cream. The product, enhanced in the antiinflammatoryeffect of glycyrrhizinic acid by the saccharide derivatives ofα,α-trehalose, is advantageously used for preventing the stimulation oritch on skins, or treating or preventing chromatophathy such as liverspot, freckling and sunburn, and aging of skins. The manner ofdissolving in combination of saccharide derivatives of α,α-trehalose andgums as this example improves the water-solubility of the gums andenables to more efficiently produce cosmetic creams than the manner ofdissolving the saccharide derivatives of α,α-trehalose within aqueousphase ingredients.

EXAMPLE 29

Night Cream

Four parts by weight of cetanol, seven parts by weight of vaseline, 21parts by weight of squalane, 2.2 parts by weight of monoglycerylstearate, 2.8 parts by weight of polyoxyethylene(20) sorbitanmonostearate, six parts by weight of isopropyl myristate, 0.3 part byweight of ethylparaben, 0.2 part by weight of perfumeries, 10 parts byweight of propylene glycol, five parts by weight of 1,3-butylene glycol,0.1 part by weight of glycyrrhetin, three parts by weight of the powdercontaining saccharide derivatives of α,α-trehalose, prepared in Example7, and an appropriate amount of deionized water to give a final weightof 100 parts in order to obtain a night cream. The product, enhanced inthe antiinflammatory effect of glycyrrhetin by the saccharidederivatives of α,α-trehalose, is advantageously used for preventingrough skins, stimulation or itch on skins. Since the product has a lowstimulation against skins and a satisfactory moisturizing effect givenby the saccharide derivatives of α,α-trehalose, it can be used withoutcare of hypersensitivity. The product is a cream having a satisfactoryskin feeling without sticky feeling when applied on skins.

EXAMPLE 30

Hand Cream

20.0 parts by weight of the syrup containing saccharide derivatives ofα,α-trehalose, prepared in Example 6, 2.0 parts by weight of urea, 2.5parts by weight of POE(60) glyceryl isostearate, 1.5 parts by weight ofmonoglyceryl stearate, four parts by weight of cetanol, 2.0 parts byweight of vaseline, 10 parts by weight of liquid paraffin, 0.01 part byweight of 2-ethylhexyl-4-tetra-butyl-4-methoxybenzoylmethaneparaoxycinnamate, 0.2 part by weight of vitamin E acetate, 0.1 part byweight of vitamin D and an appropriate amount of purified water to givea final weight of 100 parts in order to a hand cream. The product,enhanced in the blood flow-promoting effect and/or antiinflammatoryeffect of vitamin E acetate by the saccharide derivatives ofα,α-trehalose, is advantageously used for preventing rough skins,stimulation or itch on skins and preventing a damage by UV. Since theproduct has a low stimulation against skins and a satisfactorymoisturizing effect given by the saccharide derivatives ofα,α-trehalose, it can be used without care of hypersensitivity. Theproduct is a cream having a satisfactory skin feeling without stickyfeeling when applied on skins.

EXAMPLE 31

Milky Lotion

2.5 parts by weight of stearic acid, 1.5 parts by weight of cetanol,five parts by weight of vaseline, 10 parts by weight of liquid paraffin,two parts by weight of polyoxyethylene oleate, 0.5 parts by weight oftocopherol acetate, 0.2 part by weight of dipotassium glycyrrhizinate,three parts by weight of polyethylene glycol(1500), three parts byweight of ethyl L-ascorbate, three parts by weight of indigo aqueousextract, two parts by weight of arbutin, one part by weight of “αGRUTIN”, a glycosyl rutin commercialized by Hayashibara BiochemicalLaboratories, Inc., Okayama, Japan, one part by weight oftriethanolamine, two parts by weight of the syrup containing saccharidederivatives of α,α-trehalose, prepared in Example 6, 66 parts by weightof purified water and 0.1 part by weight of propylparaben were mixedtogether, adjusted to pH 6.7 with potassium hydroxide, and admixed anappropriate amount of perfumeries in a usual manner to obtain a milkylotion. The product, enhanced in the antiinflammatory effect of indigoaqueous extract by the saccharide derivatives of α,α-trehalose, isadvantageously used for alleviating or preventing inflammatory symptomsuch as stimulation or itch on skins, treating or preventing aging ofskins. Since the product has a low stimulation against skins and asatisfactory moisturizing effect given by the saccharide derivatives ofα,α-trehalose, it is a cream having a satisfactory skin feeling withoutsticky feeling when applied on skins.

EXAMPLE 32

Milky Lotion

2.5 parts by weight of stearic acid, 1.5 parts by weight of cetanol,five parts by weight of vaseline, 10 parts by weight of liquid paraffin,two parts by weight of polyoxyethylene(10) oleate, 0.1 part by weight ofpropylparaben, 0.5 part by weight of dl-α-tocopherol acetate, 0.2 partby weight of perfumeries, three parts by weight of polyoxyethyleneglycol(1500), one part by weight of triethanolamine, two parts by weightof “AA2G®”, an L-ascorbic acid 2-glucoside commercialized by HayashibaraBiochemical Laboratories, Inc., Okayama, Japan, two parts by weight ofthe syrup containing saccharide derivatives of α,α-trehalose, preparedin Example 6, and appropriate amount of deionized water to give a finalweight of 100 parts in order to obtain a milky lotion. The product,enhanced in the blood flow-promoting effect of dl-α-tocopherol acetateby the saccharide derivatives of α,α-trehalose, is advantageously usedfor preventing the stimulation or itch on skins, or treating orpreventing chromatophathy such as liver spot, freckling and sunburn, andaging of skins. Since the product has a satisfactory moisturizing effectgiven by the saccharide derivatives of α,α-trehalose, it is a creamhaving a satisfactory skin feeling without sticky feeling when appliedon skins.

EXAMPLE 33

Skin Lotion

0.2 part by weight of dipotassium glycyrrhizinate, 0.1 part by weight ofcitric acid, 0.3 part by weight of sodium citrate, 2.0 parts by weightof the syrup containing saccharide derivatives of α,α-trehalose,prepared in Example 6, 5.0 parts by weight of ethanol, 0.0001 part byweight of Kanko-so No. 201, 0.1 part of ethylparaben and an appropriateamount of water to give a final weight of 100 parts were mixed togetherto obtain a skin lotion. The product, enhanced in the antiphlogisticeffect of glycyrrhizinic acid by the saccharide derivatives ofα,α-trehalose, is advantageously used for preventing rough skins,stimulation or itch on skins. Since the product has a low stimulationagainst skins and a satisfactory moisturizing effect given by thesaccharide derivatives of α,α-trehalose, it can be used without care ofhypersensitivity. The product is a cream having a satisfactory skinfeeling without sticky feeling when applied on skins.

EXAMPLE 34

Cosmetic Essence

0.5 part by weight of polyoxyethylene sorbitol tetraoleate, 1.0 part byweight of squalane, 0.3 part by weight of xanthane gum, 0.2 part byweight of hydroxyethylcellulose, 3.0 parts by weight of the syrupcontaining saccharide derivatives of α,α-trehalose, prepared in Example6, 0.05 part by weight of sodium hyaluronate, 1.0 part by weight of “αGRUTIN”, a glycosyl rutin commercialized by Hayashibara BiochemicalLaboratories, Inc., Okayama, Japan, 0.1 part by weight of disodiumedetate, 0.5 part by weight of indigo aqueous extract, 0.1 part byweight of ethylparaben, and appropriate amount of water to give a finalweight of 100 parts were mixed and dissolved together in a usual mannerto obtain a cosmetic essence. The product, enhanced in theantiinflammatory effect of indigo aqueous extract by the saccharidederivatives of α,α-trehalose, is advantageously used for preventingrough skins, stimulation or itch on skins, and treating and preventingaging of skins. Since the product has a low stimulation against skinsand a satisfactory moisturizing effect given by the saccharidederivatives of α,α-trehalose, it is a cream having a satisfactory skinfeeling without sticky feeling when applied on skins. The saccharidederivatives of α,α-trehalose and/or glycosyl rutin inhibit theoxidation, decomposition and denaturation of co-existing baseingredients for external dermatological formulation, substances havingemulsifying effect, perfumeries or colorants, they inhibit the browning,discoloration and generation of foreign smell in a long period.Therefore, the product keeps its quality for a long period.

EXAMPLE 35

Cosmetic Essence

0.5 part by weight of polyoxyethylene sorbitol tetraoleate, 1.0 part byweight of squalane, 0.3 part by weight of xanthane gum, 0.2 part byweight of hydroxyethylcellulose, 3.0 parts by weight of the syrupcontaining saccharide derivatives of α,α-trehalose, prepared in Example6, two parts by weight of L-ascorbic acid, 0.05 part by weight of sodiumhyaluronate, 1.0 part by weight of “αG RUTIN”, a glycosyl rutincommercialized by Hayashibara Biochemical Laboratories, Inc., Okayama,Japan, 1.0 part by weight of “αG HESPERIDIN”, a glycosyl hesperidincommercialized by Hayashibara Biochemical Laboratories, Inc., Okayama,Japan, 0.1 part by weight of disodium edetate, 0.5 part by weight ofindigo aqueous extract, 0.1 part by weight of ethylparaben, andappropriate amount of water to give a final weight of 100 parts weremixed and dissolved together, and adjusted to about pH 6.8 withpotassium hydroxide in a usual manner to obtain a cosmetic essence. Theproduct, enhanced in the antiinflammatory effect of indigo aqueousextract and blood flow-promoting effect of glycosyl rutin and glycosylhesperidin by the saccharide derivatives of α,α-trehalose, isadvantageously used for preventing rough skins, stimulation or itch onskins, and treating and preventing aging of skins. Since the product hasa low stimulation against skins and a satisfactory moisturizing effectgiven by the saccharide derivatives of α,α-trehalose, it is a cosmeticessence having a satisfactory skin feeling without sticky feeling whenapplied on skins. The saccharide derivatives of α,α-trehalose and/orglycosyl rutin inhibit the oxidation, decomposition and denaturation ofit or substances having emulsifying effect and perfumeries, they inhibitthe browning, discoloration and generation of foreign smell. Therefore,the product is inhibited in the deterioration of quality for a longperiod.

EXAMPLE 36

Lotion

Twenty parts by weight of 1% sodium hyaluronate aqueous solution, twoparts by weight of the saccharide derivatives of α,α-trehalose, preparedin Example 6, 2.1 parts by weight of 60% sorbitol aqueous solution, 0.5part by weight of glycyrrhiza extract, 0.05 part by weight of chamomileextract, 1.0 part by weight of sage extract, 0.001 part by weight ofaloe extract powder, 0.02 part by weight of citric acid, 0.18 part byweight of sodium citrate, 0.05 part by weight of methyl paraoxybenzoateand an appropriate amount of water to give a final weight of 100 partswere mixed together to obtain a lotion. The product, enhanced in theantiphlogistic effect of glycyrrhiza extract by the saccharidederivatives of α,α-trehalose, is advantageously used for preventingrough skins, stimulation or itch on skins, and treating and preventingaging of skins. Since the product has a low stimulation against skinsand a satisfactory moisturizing effect given by the saccharidederivatives of α,α-trehalose, it is a lotion having a satisfactory skinfeeling without sticky feeling when applied on skins.

EXAMPLE 37

Mudpack

9.0 parts by weight of bentonite, 14.0 parts by weight of kaolin, 1.0part by weight of polyoxyethylene sorbitan monostearate, 10.0 parts byweight of the syrup containing saccharide derivatives of α,α-trehalose,prepared in Example 6, 0.35 part by weight of dipotassiumglycyrrhizinate, 3.0 parts by weight of indigo aqueous extract, 0.1 partby weight of ethylparaben, 5.0 parts by weight of ethanol, 10.0 parts byweight of polyethylene glycol, and 47.5 parts by weight of water wereheated and homogeneously mixed together to obtain a mudpack. Theproduct, enhanced in the antiphlogistic effect of glycyrrhizinic acid bythe saccharide derivatives of α,α-trehalose, is advantageously used forpreventing rough skins, stimulation or itch on skins, and treating andpreventing aging of skins. Since the product has a low stimulationagainst skins and a satisfactory moisturizing effect given by thesaccharide derivatives of α,α-trehalose, it is a lotion having asatisfactory skin feeling without sticky feeling when applied on skins.

EXAMPLE 38

Gel Cream for Sun-Protect

4.0 parts by weight of octyl paramethoxy cinnamate, 3.0 parts by weightof oxybenzon, 16.0 parts by weight of liquid paraffin, 9.0 parts byweight of olive oil and 0.01 part by weight of dibutylhydroxytoluenewere heated and mixed together, and admixed with 1.0 part by weight ofthe syrup containing saccharide derivatives of α,α-trehalose, preparedin Example 6, 0.6 part by weight of acrylic acid/alkyl methacrylateco-polymer, 0.4 part by weight of carboxyvinylpolymer, 2.0 parts byweight of “AA2G®”, an L-ascorbic acid 2-glucoside commercialized byHayashibara Biochemical Laboratories, Inc., Okayama, Japan, 1.0 part byweight of allantoin, 1.0 part by weight of triethanolamine, andappropriate amounts of antiseptics and water to give a final weight of100 parts, and emulsified in a usual manner to obtain a cream. Theproduct, enhanced in the antiinflammatory effect of allantoin by thesaccharide derivatives of α,α-trehalose, is a gel having a satisfactoryantiphlogistic effect to prevent sunburn and alleviating burning. Sincethe product has a satisfactory moisturizing effect given by thesaccharide derivatives of α,α-trehalose, it has a satisfactory skinfeeling without sticky feeling when applied on skins. The product,lowered in the stimulation against skins by the effect of saccharidederivatives of α,α-trehalose, gives a relatively-low pain to skins evenwhen applied to sunburned skin. It prevents aging of skins due to UV,and is a gentle gel cream to skins.

EXAMPLE 39

Gel for Sun-Protect

1.0 part by weight of “AQUPEC HV505”, a polyacrylate type polymercommercialized by Sumitomo Seika Chemicals Co., Ltd., Osaka, Japan,dispersed in an appropriate amount of purified water heated at about 55°C. and cooled to below 40° C., was admixed with 2.0 parts by weight of“AA2G®”, an L-ascorbic acid 2-glucoside commercialized by HayashibaraBiochemical Laboratories, Inc., Okayama, Japan, dissolving in anappropriate amount of water, and further admixed with 0.9 part by weightof potassium-hydroxide to be adjusted to pH6.3. The resulting mixturewas admixed with 2.0 parts by weight of saccharide derivatives ofα,α-trehalose, prepared in Example 6, 4.0 parts by weight ofconcentrated glycerin, 2.0 parts by weight of 1,3-butylene glycol, 3.0parts by weight of dipropylene glycol, two parts by weight of “αGHESPERIDIN”, a glycosyl hesperidin commercialized by HayashibaraBiochemical Laboratories, Inc., Okayama, Japan, 1.3 parts by weight ofsorbitol, 1.5 parts by weight of polyethylene glycol(400), 3.1 parts byweight of 1,2-pentanediol and 0.5 part by weight of glycyrrhetinic acid,dissolved, and further admixed with purified water to give a finalweight of 100 parts in order to obtain a gel for sun-protect. Theproduct, enhanced in the antiinflammatory effect of glycyrrhetinic acidand L-ascorbic acid 2-glucoside by the saccharide derivatives ofα,α-trehalose, is a gel having a satisfactory antiphlogistic effect toprevent sunburn and alleviating burning. Since the product has asatisfactory moisturizing effect given by the saccharide derivatives ofα,α-trehalose, it has a satisfactory skin feeling without sticky feelingwhen applied on skins. In addition, the product, containing dipropyleneglycol and polyethylene glycol, is kept at pH 5.9-7.0 by addingpotassium hydroxide. The product is a transparent gel having asatisfactory skin feeling without occurrence of kink or dirtcharacteristic to the gel containing L-ascorbic acid 2-glucoside. Theproduct is a so stable gel that it does not show the change of pH,reduction of viscosity, and coloring even when preserved for a longperiod. The product, lowered in the stimulation against skins by theeffect of saccharide derivatives of α,α-trehalose, gives arelatively-low pain to skins even when applied to sunburned skin. Itprevents aging of skins due to UV, and is a gentle gel cream to skins.

EXAMPLE 40

Gel for Preventing Aging

51.3 parts by weight of trioctalein, 16.4 parts by weight of the syrupcontaining saccharide derivatives of α,α-trehalose, prepared in Example6, 14.5 parts by weight of purified water, 8.7 parts by weight ofglycerol, 5.2 parts by weight of polyglyceryl(10) monomyristate, 1.75parts by weight of polyglyceryl(10) monostearate, one part by weight of“AA2G®”, an ascorbic acid 2-glucoside commercialized by HayashibaraBiochemical Laboratories, Inc., Okayama, Japan, two parts by weight of“αG RUTIN”, a glycosyl rutin commercialized by Hayashibara BiochemicalLaboratories, Inc., Okayama, Japan, and 0.1 part by weight ofmethylparaben were used in a usual manner to obtain a gel. The product,lowered in the stimulation against skins by the effect of saccharidederivatives of α,α-trehalose, gives a relatively-low pain to skins evenwhen applied to sunburned skin. It prevents aging of skins due to UV,and is a gentle gel cream to skins.

EXAMPLE 41

Cleansing Foam

A cleansing foam was produced by adding following ingredients in a usualmanner; 14 parts by weight of myristic acid, nine parts by weight ofpalmitic acid, seven parts by weight of stearic acid, parts by weight ofthe syrup containing saccharide derivatives of α,α-trehalose, preparedin Example 6, three parts by weight of polyethylene glycol(4000), twoparts by weight of ethylene glycol distearate, six parts by weight ofpolyethylene glycol distearate(140 E.O.), four parts by weight ofdiethanolamide laurate, 0.4 part by weight of methyl paraoxybenzoate,0.1 part by weight of tocopherol, 6.3 parts by weight of potassiumhydroxide, 30% aqueous solution of amidepropyl betaine laurate, and 26.2parts by weight of purified water. The product, enhanced in theantiinflammatory effect of tocopherol by the saccharide derivatives ofα,α-trehalose, is a foam having a satisfactory antiphlogistic effect toprevent sunburn and alleviating burning. Since the product has asatisfactory moisturizing effect given by the saccharide derivatives ofα,α-trehalose, it has a satisfactory skin feeling without sticky feelingwhen applied on skins.

A cleansing foam was prepared in the same manner to Example 41 exceptfor using five parts by weight of sorbitol, as an ingredient of usualcleansing foams, instead of five parts by weight of saccharidederivatives of α,α-trehalose. The cleansing foam prepared above and thecleansing foam containing saccharide derivatives of α,α-trehalose,prepared in Example 40, were compared in view of bubble height of justafter bubbling and five minutes later from bubbling according to RossMiles method. The result is shown in Table 16. TABLE 16 Height of bubble(mm) Just after Five minutes Cleansing foam bubbling after bubblingContaining 7% of the syrup 198 171 containing saccharide derivatives ofα,α-trehalose Containing 7% sorbitol 186 160

As evidence from the result shown in Table 16, the cleansing foamcontaining the saccharide derivatives of α,α-trehalose showed higherbubble height of both of just after bubbling and five minutes later thanthe cleansing foam containing sorbitol. In addition, the former was alsosuperior in view of the production and retain of bubble. The resultreveals that saccharide mixture containing saccharide derivatives ofα,α-trehalose more imparts elasticity to bubble of cleansing foams thansorbitol and is capable of improving the property of bubble.

EXAMPLE 42

Shampoo

Thirty five parts by weight of 30%2-alkyl-N-carboxymethyl-N-hydroxymethyl imidazolium betaine aqueoussolution, 35 parts by weight of 30% triethanolamine cocoylglutamateaqueous solution, 10 parts by weight of the syrup containing saccharidederivatives of α,α-trehalose, prepared in Example 6, 10 parts by weightof 30% potassium cocoylglycine aqueous solution, 2.3 parts by weight ofdiethanolamide cocoate, three parts by weight of “αG HESPERIDIN”, aglycosyl hesperidin commercialized by Hayashibara BiochemicalLaboratories, Inc., Okayama, Japan, 0.005 part by weight of Kanko-so No.201, 0.005 parts by weight of Kanko-so No. 301, and 10 parts by weightof purified water were mixed together, heat-dissolved to 70° C. withstirring, and admixed with an appropriate amount of perfumeries in ausual manner to obtain a shampoo. The product, enhanced in the bloodflow-promoting effect of glycyrrhizinic acid by the saccharidederivatives of α,α-trehalose, is advantageously used for preventing itchof head skins, production of scurf, hair growing, hair nourishing, andtreating and preventing aging of skins. Since the product has asatisfactory moisturizing effect given by the saccharide derivatives ofα,α-trehalose in spite of without glycerin, it is a shampoo having asatisfactory skin feeling without sticky feeling.

EXAMPLE 43

Hair Conditioner

2.5 parts by weight of liquid paraffin, 0.5 parts by weight of myristicacid, 1.5 parts by weight of cetanol, three parts by weight of glycerinmonostearate, one part by weight of di-polyoxyethylene 2-octyldodecylN-lauroyl glutamate and 0.5 part by weight of polyoxyethylene glycerylmonopyroglutamate monoisostearate were heated and mixed together. Theresulting mixture was admixed with three parts by weight of the syrupcontaining saccharide derivatives of α,α-trehalose, prepared in Example6, three parts by weight of 1,3-butylene glycol, 0.01 part by weight ofKanko-so No. 301, 2.5 parts by weight of lauroyl-L-lysine, 0.5 part byweight of fatty acid L-arginine ethylpyrolydon carbonate, 0.5 part byweight of stearyl trimethyl ammonium chloride, 0.1 part by weight of “αGRUTIN”, a glycosyl rutin commercialized by Hayashibara BiochemicalLaboratories, Inc., Okayama, Japan, one part by weight of sodiumpyrrolidone carbonate, one part by weight of sialid extract, and 74parts by weight of purified water with heating, and emusified in a usualmanner to obtain a hair conditioner. The product, enhanced in the bloodflow-promoting effect of sialid extract by the saccharide derivatives ofα,α-trehalose, is advantageously used for preventing itch of head skins,production of scurf, hair growing, hair nourishing, and treating andpreventing aging of skins. Since the product has a satisfactorymoisturizing effect given by the saccharide derivatives of α,α-trehalosein spite of without glycerin, it is a hair conditioner having asatisfactory skin feeling without sticky feeling.

EXAMPLE 44

Hair Treatment

Five parts by weight of stearyl alcohol, five parts by weight ofglycerin monostearate, 3.5 parts by weight of liquid paraffin, two partsby weight of di-polyoxyethylene 2-octyldodecyl N-lauroyl glutamate andone part by weight of polyoxyethylene glyceryl monopyroglutamatemonoisostearate were heated and mixed together. The resulting mixturewas admixed with five parts by weight of the syrup containing saccharidederivatives of α,α-trehalose, prepared in Example 6, three parts byweight of 1,3-butylene glycol, one part by weight ofstearyltrimethylammonium chloride, one part by weight of sodiumpyrrolidone carbonate, 0.1 part by weight of dl-tocopherol, 0.1 part byweight of keratin polymer, and 65 parts by weight of deionized waterwith heating, and emulsified in a usual manner to obtain a hairtreatment. The product, enhanced in the blood flow-promoting effect ofdl-tocopherol by the saccharide derivatives of α,α-trehalose, isadvantageously used for preventing itch of head skins, production ofscurf, hair growing, hair nourishing, and treating and preventing agingof skins. Since the product has a satisfactory moisturizing effect givenby the saccharide derivatives of α,α-trehalose in spite of withoutglycerin, it is a hair treatment having a satisfactory skin feelingwithout sticky feeling.

EXAMPLE 45

Body Soap

Fifteen parts by weight of potassium laurate, 5.0 parts by weight ofpotassium myristate, 4.0 parts by weight of the syrup containingsaccharide derivatives of α,α-trehalose, prepared in Example 6, 2.0parts by weight of propylene glycol, 1.0 part by weight of chamomileextract, 0.5 part by weight of polyethylene powder, 0.5 part by weightof hydroxypropyl chitosan solution, 0.25 part by weight of glycine, 0.25part by weight of glutamine, 0.2 part by weight of azulene, 0.1 part byweight of Kanko-so No. 201; an appropriate amount of pH-controllingagent and lavender water. The resulting mixture was admixed withpurified water to give a final weight of 100 parts and emulsified in ausual manner in order to body soap. The product, enhanced in theantiinflammatory effect of azulene by the saccharide derivatives ofα,α-trehalose, is advantageously used for preventing itch of skins, andtreating or preventing aging of skins. Since the product has asatisfactory moisturizing effect given by the saccharide derivatives ofα,α-trehalose in spite of without glycerin, it is a body soap having asatisfactory skin feeling without sticky feeling.

EXAMPLE 46

Cleansing Oil

20.0 parts by weight of jojoba oil, 15.0 parts by weight of macadamianut oil, 15.0 parts by weight of liquid paraffin, 9.0 parts by weight ofcetyl isooctanoate, 20.0 parts by weight of POE(20) glycerintriisostearate, 10.0 parts by weight of POE(20) glycerinmonoisostearate, 10.0 parts by weight of purified water, 0.1 part byweight of vitamin E and 1.0 part by weight of the powder containingsaccharide derivatives of α,α-trehalose were mixed in a usual manner toobtain a cleansing oil. The product, enhanced in the antiinflammatoryeffect and/or blood flow-promoting effect of vitamin E by the saccharidederivatives of α,α-trehalose, has effects on preventing itch of skins,and treating and preventing aging of skins as well as cleansing effect.Therefore, it is advantageously used as a cosmetic for massage and bathoil. Since the product has a satisfactory moisturizing effect and a lowstimulation against skins given by the saccharide derivatives ofα,α-trehalose, it is a cleansing oil having a satisfactory skin feelingwithout sticky feeling. In addition, the product, improved in thestability of unsaturated fatty acids during preservation, has anadvantage to suppress the generation of foreign odor and discoloration.

EXAMPLE 47

Cleansing Powder

Forty six parts by weight of a powder containing saccharide derivativesof α,α-trehalose, produced by spray-drying the syrup prepared in Example6 in a usual manner, 40 parts by weight of glucose, seven parts byweight of carboxy methylcellulose, one part by weight of “BIOECOLIA”, amaltose-sucrose condensate commercialized by Nikko Chemicals, Co., Ltd.,Tokyo, Japan, one part by weight of “AA2G®”, an L-ascorbic acid2-glucoside commercialized by Hayashibara Biochemical Laboratories,Inc., Okayama, Japan, 0.1 part by weight of allantoin, 0.2 part byweight of the powder prepared above in this Example containing 1,000units/g of “LIPASE MY-30”, a lipase (30,000 units/g) commercialized byMeito Sangyo Co., Ltd., Aichi, Japan, 0.002 part by weight of Kanko-soNo. 401 and one part by weight of the powder prepared above in thisExample above containing 5 units/g of “BIOPRASE CONC”, a protease(150,000 units/g) commercialized by Nagase Chemtex Corporation, Osaka,Japan, were mixed together, and passed through a 26-mesh sieve tohomogeniety to obtain a powdery product. The product, enhanced in theantiphlogistic effect of allantoin by the saccharide derivatives ofα,α-trehalose, has effects on preventing itch of skins, and treating andpreventing aging of skins as well as it is effective on removingexcessive sebum and old keratin from facial skins. Therefore, it isadvantageously used for preventing stimulation or itch of skins, andtreating or preventing aging of skins. Since the product has asatisfactory moisturizing effect given by the saccharide derivatives ofα,α-trehalose in spite of without glycerin, it is a cleansing powderhaving a satisfactory skin feeling without tightening feeling afterapplied.

EXAMPLE 48

Mouse Wash

Fifteen parts by weight of ethanol, 10 parts by weight of the syrupcontaining saccharide derivatives of α,α-trehalose, prepared in Example1, one part by weight of “αG HESPERIDIN”, a glycosyl hesperidincommercialized by Hayashibara Biochemical Laboratories, Inc., Okayama,Japan, two parts by weight of polyoxyethylene caster wax, 0.02 part byweight of saccharine-Na, 0.05 part by weight of sodium benzoate, 0.1part by weight of sodium dihydrogenphosphate, appropriate amount ofcolorants and perfumeries, and 72.2 parts by weight of water were mixedtogether to obtain a mouth wash. The product, enhanced in the bloodflow-promoting effect of glycosyl hesperidin by the saccharidederivatives of α,α-trehalose, has effects on improving dry mouth due toSjogren syndrome, and preventing or treating oral inflammations anddysgeusia. In addition, it is a mouth wash having a satisfactory skinfeeling.

EXAMPLE 49

Toothpaste

Thirty parts by weight of dipotassium hydrogen phosphate, 10 parts byweight of hydroxyapatite, five parts by weight of calcium carbonate, 30parts by weight of the syrup containing saccharide derivatives ofα,α-trehalose, prepared in Example 1, 1.5 parts by weight of sodiumrauryl sulfate, 0.7 part by weight of sodium monofluorophosphate, 0.5part by weight of polyoxyethylene sorbitan raurate, 0.5 part by weightof diphenhydramine hydrochloride, 0.05 part by weight of antiseptics, 22parts by weight of purifies water were mixed together to obtain atoothpaste. The product, enhanced in the blood flow-promoting effect ofdiphenhydramine hydrochloride by the saccharide derivatives ofα,α-trehalose, has effects on preventing or treating oral inflammationsand dysgeusia, or swelling, inflammation and bleeding of teethridge dueto alveolar pyorrhea. In addition, it is a toothpaste having asatisfactory skin feeling.

EXAMPLE 50

Toothpaste

Thirty parts by weight of dipotassium hydrogen phosphate, 10 parts byweight of hydroxyapatite, five parts by weight of calcium carbonate, 30parts by weight of the syrup containing saccharide derivatives ofα,α-trehalose, prepared in Example 1, 2.0 parts by weight of propolisextract, 1.5 parts by weight of sodium rauryl sulfate, 1.5 parts byweight of glycyrrhiza extract, 1.0 part by weight of “αG HESPERIDIN”, aglycosyl hesperidin commercialized by Hayashibara BiochemicalLaboratories, Inc., Okayama, Japan, 0.7 part by weight of sodiummonofluorophosphate, 0.5 part by weight of polyoxyethylene sorbitanraurate, 0.5 part by weight of antiseptics, 19 parts by weight ofpurifies water were mixed together to obtain a toothpaste. The product,enhanced in the antiinflammatory effect of glycyrrhizia extract and theblood flow-promoting effect of glycosyl hesperidin by the saccharidederivatives of α,α-trehalose, which are non-cariogenetic saccharides andhardly produce water-insoluble glucans with acidic fermentation and hasan anticarious effect on inhibiting the production of water-insolubleglucans from sucrose, has effects on preventing dental caries, andpreventing or treating oral inflammations and dysgeusia, or swelling,inflammation and bleeding of teethridge due to alveolar pyorrhea. Inaddition, it is a toothpaste having a satisfactory skin feeling.

EXAMPLE 51

Kitchen Detergent

Twenty one parts by weight of a surfactant composition consisting ofsodium alkylalanine methylalanine alkylamidepropylbetaine and fatty aciddiethanolamide, five parts by weight of the powder containing saccharidederivatives of α,α-trehalose, prepared in Example 7, 0.1 part by weightof vitamin E, and appropriate amounts of polyoxyethylene alkyl ether,perfumeries and colorants were mixed together to obtain a kitchendetergent. The product, having a strong detergency and enhanced in theantiphlogistic effect of vitamin E by the saccharide derivatives ofα,α-trehalose, has an effect on preventing rough skins due to usingdetergents. The product has not only satisfactory moisturizing effect,but also it is capable of suppressing in the defatting due tosurfactants, denaturation of corneous proteins, and permeability ofskins by an skin protecting effect of saccharide derivatives ofα,α-trehalose therein. The product is a kitchen detergent having aninhibitory effect on skin disorders such as rough skins of hands, etc.,and a satisfactory skin feeling without tightening feeling afterapplied. In addition, the product can be advantageously used foralleviating pains or disorders due to insect bite and sting, orcontacting to a kind of poisonous moth or larva thereof in a manner ofapplied on the skins.

EXAMPLE 52

Ointment for Treating External Injuries

450 parts by weight of macrogol (400), three parts by weight ofcarboxyvinylpolymer, one part by weight of pullulan, 400 parts by weightof isopropanol, one part by weight of chlorhexidine gluconate solutionand 10 parts by weight of indomethacin were mixed in vacuo. Theresulting mixture was admixed with 70 parts by weight of the powdercontaining saccharide derivatives of α,α-trehalose, prepared in Example3, three parts by weight of sodium hydroxide and 77 parts by weight ofpurified water to obtain a ointment for treating external injuries withan appropriate extension and adherence. The product, enhanced in theantiinflammatory effect of indomethacin by the saccharide derivatives ofα,α-trehalose, is capable of treating external injuries accompanyingitches and pains of cuts, grazes, burns, athlete's foot or frostbites ina manner of applying directly or with a gauze to such a wounded surface.The product, containing saccharide derivatives of α,α-trehalose, is anointment for treating external injuries having a satisfactory skinfeeling without sticky feeling.

INDUSTRIAL APPLICABILITY

The external dermatological formulation of the present inventioncontains safe and extremely stable saccharide derivatives ofα,α-trehalose and a substance having any one of blood flow-promotingeffect, antiinflammatory effect, antibacterial effect, moisturizingeffect, whitening effect, UV-absorbing effect, UV-scattering effect,antioxidant effect, hairing effect, hair nourishing effect, astringenteffect, wrinkle-reducing effect, cell-activating effect and transdermalabsorption-promoting effect as effective ingredients. The formulationhas a satisfactory skin feeling without sticky feeling, and is enhancedin the effects of effective ingredients by saccharide derivatives ofα,α-trehalose. Therefore, it is used in the various fields such ascosmetics, quasi-drugs, pharmaceuticals and gloceries.

The present invention with such as outstanding function and effect is asignificant invention that will greatly contribute to this art.

1-51. (canceled)
 52. A saccharide composition, which comprises 5% ormore of α-maltosyl α,α-trehalose, on a dry solid basis. 53-54.(canceled)
 55. The saccharide composition of claim 52, which comprises 5to 25% of other saccharide derivatives of α,α-trehalose than α-maltosylα,α-trehalose, on a dry solid basis.
 56. The saccharide composition ofclaim 55, which comprises 25 to 45% of sugar alcohols, on a dry solidbasis.
 57. A process for producing the saccharide composition of claim56, which comprises i) reacting a starch material with a non-reducingsaccharide-forming enzyme; and ii) hydrogenating the resulting mixture.58-64. (canceled)
 65. An external dermatological formulation, comprisingthe saccharide composition of claim 52 and at least one substanceselected from the group consisting of an antioxidant, detergent,substance having anti-inflammatory effect, substance having blood flowpromoting effect and substance having moisturizing effect.
 66. Theexternal dermatological formulation of claim 65, wherein saidantioxidant is ascorbic acid or a derivative thereof, wherein saiddetergent is sodium dodecyl sulfate, wherein said substance havingantiinflammatory effect is glycyrrhizinic acid or a derivative thereof,wherein said substance having blood flow promoting effect is tocopherolor a derivative thereof, hesperidin or a derivative thereof, rutin or aderivative thereof, sialid extract, or ginseng extract, or wherein saidsubstance having moisturizing effect is hyaluronic acid or a derivativethereof.
 67. A process of the external dermatological formulation ofclaim 65 or 66, which comprises a step of incorporating said saccharidecomposition in an external dermatological formulation containing asubstance selected from the group consisting of antioxidant, detergent,substance having antiinflammatory effect, substance having blood flowpromoting effect and substance having moisturizing effect.
 68. A methodfor inhibiting the browning of ascorbic acid or a derivative thereof,which comprises incorporating the saccharide composition of claim 52 insaid ascorbic acid or derivatives thereof.
 69. A method for improvingthe foaming property of a detergent, which comprises incorporating thesaccharide composition of claim 52 in a detergent.
 70. A method forpreventing or inhibiting inflammation of skin, which comprises applyingthe saccharide composition of claim 52 to the skin.
 71. The method ofclaim 70, wherein said inflammation of skin is rough skin.
 72. Themethod of claim 70 or 71, which further comprises applying anantiinflammatory substance to the skin.
 73. A method for preventing theelectrification of skin, which comprises applying the saccharidecomposition of claim 52 to the skin.
 74. A method for activating orprotecting cells, which comprises a step of applying the saccharidecomposition of claim 52 to the cells.
 75. A method for preventing orinhibiting dental caries, which comprises applying the saccharidecomposition of claim 52 to teeth.
 76. A method for promoting blood flowin skin, which comprises applying the saccharide composition of claim 52and a substance having blood flow promoting effect to the skin.
 77. Amethod for moisturizing skin, which comprises applying the saccharidecomposition of claim 52 and a substance having moisturizing effect tothe skin.